bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconciling Nation and Class in Imperial Borderlands: the Making of Bolshevik Internationalists Karl Radek and Feliks Dzierżyński in East Central Europe1
Authors: RIGA LILIANA
Published: November 2006

Abstract  This article interprets the biographies of Polish Bolshevik revolutionaries, Feliks Dzierżyński and Karl Radek, in an attempt to concretize socialism's “nationalities problem” in two exceptional, but emblematic, identities of the fin‐de‐siècle socialist movement. It situates their internationalism against the sociology of nationalism in multiethnic imperial borderlands. It argues that the appeal of socialist internationalism was contingent on the strength of nationalism: where nationalism was more politically articulate it undermined universalist ideologies. Therefore as socialism succeeded in transcending ethnonational boundaries only in the Tsarist Russian “fourth time zone”, Radek and Dzierżyński traveled eastwards from Polish nationalism to Bolshevik internationalism.
Assessing the Power of the Purse: An Index of Legislative Budget Institutions
Authors: Wehner Joachim
Published: November 2006

To compare parliamentary capacity for financial scrutiny, I construct an index using data for 36 countries from a 2003 survey of budgeting procedures. The index captures six institutional prerequisites for legislative control, relating to amendment powers, reversionary budgets, executive flexibility during implementation, the timing of the budget, legislative committees and budgetary information. Various methods of index construction are reviewed. The results reveal substantial variation in the level of financial scrutiny of government by the legislature among contemporary liberal democracies. The US Congress has an index score that is more than three times as great as those for the bottom nine cases, predominantly Westminster systems. Even allowing for US exceptionalism, the top quartile of legislatures score twice as high on this index as the bottom quartile. These findings suggest that the power of the purse is a discrete and non-fundamental element of liberal democratic governance. For some countries it is a key safeguard against executive overreach, while others maintain a constitutional myth.
Alternative Ulster? Political Parties and the Non-Constitutional Policy Space in Northern Ireland
Authors: Lutz Karin Gilland , Farrington Christopher
Published: November 2006

This article uses data from a survey of the candidates in the 2003 Northern Ireland Assembly election to measure the policy positions of the Northern Irish political parties on scales that are the usual measurements of party policy in Western Europe, such as on economic and social issues, the European Union, morality issues, environmental issues and minority groups. These data were then used to test whether the Northern Ireland party system was conducive to integration or consociationalism, which is the current debate on conflict resolution in Northern Ireland. It argues that this debate has been under-theorised and that empirical data can be used to test the likelihood of either scenario. It concludes that, in most aspects, the Northern Ireland party system tends towards the consociational scenario but there are, nevertheless, aspects which suggest that an integrationist scenario could be produced in the long term.
The significance of place in middle childhood: qualitative research from Wales
Authors: Scourfield Jonathan , Dicks Bella , Holland Sally , Drakeford Mark , Davies Andrew
Published: November 2006

The paper presents some key findings of qualitative research with older primary school children in Wales on their attachments to places and cultures. There is discussion of children's perspectives on the global, national and local arenas. We argue both that there are continuities with adult perspectives and that the children's views on place and identity need to be understood in the context of the social location of middle childhood. The study shows children making relatively little use of culturally‐filled categories of local, national and global place‐identifications. The differences they articulate are largely framed in terms of divisions between groups of people rather than in the characteristics of place, and generally related back to the self.
Sovereignty transformed: a sociology of human rights1
Authors: Levy Daniel , Sznaider Natan
Published: November 2006

This paper examines how global interdependencies and the consolidation of a human rights discourse are transforming national sovereignty. Social researchers frequently address the supremacy of state sovereignty and the absoluteness of human rights as mutually exclusive categories. However, rather than presupposing that a universal rights discourse is necessarily leading to the demise of sovereignty, we suggest that an increasingly de‐nationalized conception of legitimacy is contributing to a reconfiguration of sovereignty itself. Through the analytic prism of historical memories – which refers to shared understandings specific pasts carry for present concerns of a political community – we provide an explanatory factor for the salience of human rights norms as a globally available repertoire of legitimate claim making. While states retain most of their sovereign functions, their legitimacy is no longer exclusively conditioned by a contract with the nation, but also by their adherence to a set of nation‐transcending human rights ideals. Legitimacy is mediated by how willing states are to engage with ‘judicial memories’ of human rights abuses and their articulation in cosmopolitan legal frames. Empirically, we focus on war crime trials and how legal inscriptions of memories of human rights abuses are recasting the jurisdiction of International Law. The readiness of states to engage with rights abuses is becoming politically and culturally consequential, as adherence to global human rights norms confers legitimacy.
Crimp morphology in relaxed and stretched rat Achilles tendon
Authors: Franchi Marco , Fini Milena , Quaranta Marilisa , De Pasquale Viviana , Raspanti Mario , Giavaresi Gianluca , Ottani Vittoria , Ruggeri Alessandro
Published: November 2006

Fibrous extracellular matrix of tendon is considered to be an inextensible anatomical structure consisting of type I collagen fibrils arranged in parallel bundles. Under polarized light microscopy the collagen fibre bundles appear crimped with alternating dark and light transverse bands. This study describes the ultrastructure of the collagen fibrils in crimps of both relaxed and in vivo stretched rat Achilles tendon. Under polarized light microscopy crimps of relaxed Achilles tendons appear as isosceles or scalene triangles of different size. Tendon crimps observed via SEM and TEM show the single collagen fibrils that suddenly change their direction containing knots. The fibrils appear partially squeezed in the knots, bent on the same plane like bayonets, or twisted and bent. Moreover some of them lose their D‐period, revealing their microfibrillar component. These particular aspects of collagen fibrils inside each tendon crimp have been termed ‘fibrillar crimps’ and may fulfil the same functional role. When tendon is physiologically stretched in vivo the tendon crimps decrease in number (46.7%) (P < 0.01) and appear more flattened with an increase in the crimp top angle (165° in stretched tendons vs. 148° in relaxed tendons, P < 0.005). Under SEM and TEM, the ‘fibrillar crimps’ are still present, never losing their structural identity in straightened collagen fibril bundles of stretched tendons even where tendon crimps are not detectable. These data suggest that the ‘fibrillar crimp’ may be the true structural component of the tendon crimp acting as a shock absorber during physiological stretching of Achilles tendon.
Microhabitat use by garden dormice during nocturnal activity
Authors: Bertolino S.
Published: November 2006

The microhabitat used by the garden dormouse Eliomys quercinus during its nocturnal activity was examined. Twenty‐three variables describing habitat structure were measured at 100 trapping points. Logistic regression models were utilized to select the variables that discriminate between used and avoided trapping points and, in a series of pairwise contrasts, between trap sites used by different sexes, age classes and animals in different reproductive periods. Used sites were characterized by a higher (>40%) rock cover, a thicker shrub layer and a younger understory with trees of smaller trunk diameter. These variables describe areas with rockfalls from the upper slope, where trees were younger and smaller, the canopy closure reduced and the shrub layer more developed than in other parts of the forest. Dense shrubby vegetation provided protection from aerial predators and, in conjunction with rocks and stones, might have made hunting by birds and mammals more difficult. Garden dormice may also have been attracted by rocky areas acting as a heat source during the night. The selection of rocky areas was more important in the first months of the active period, when animals emerged from hibernation and started the mating season. At the end of summer, the animals used areas richer in herbs, where insects and other food resources were probably more abundant.
Public Investment in Europe: Evolution and Determinants in perspective*
Authors: Mehrotra Aaron , Välilä Timo
Published: November 2006

We describe the evolution of public investment and public capital stocks in Europe over the past three decades. Against this background, we analyse the macroeconomic determinants of public investment, with a special focus on its long‐term trend. We find that public investment has been determined by national income, the stance of budgetary policies and fiscal sustainability considerations. Neither the cost of financing nor the fiscal rules embodied in EMU have had a systemic impact on public investment. The significant downtrend that characterises the evolution of public investment in non‐cohesion countries is chiefly determined by drawn‐out episodes of fiscal consolidation, unrelated to EMU.
Ignoring ‘History from Below’: People's History in the Historiography of Singapore
Authors: Song Ernest Koh Wee
Published: November 2006

The history of Singapore is widely understood as a history of its economic success. From its heyday as a nexus of trade during the imperial era to the ‘technotropolis’ that boasts high living standards for most of its citizens, Singapore as a historical subject is often viewed through the lens of the ruling elite. By expending the need to acknowledge the historical function of the citizenry in the island's socio‐economic development, the policies and personalities of the Singaporean leadership have been erroneously and simplistically used by many as an example of how the sheer genius of a few can triumph in the face of overwhelming adversity. This article seeks to trace tangents in the wider development of Singapore's historiography in order to account for the general disinterest in people's histories of Singapore.
A three‐year prospective study of adult subjects with gingivitis. I: clinical periodontal parameters
Authors: Bogren Anna , Teles Ricardo , Torresyap Gay , Haffajee Anne D. , Socransky Sigmund S. , Lindhe Jan , Wennström Jan L.
Published: November 2006

Aim: The objective of this study was to monitor prospectively clinical parameters in subjects without signs of destructive periodontal disease who were involved in a primary prevention programme, and to determine the changes that occurred between yearly examinations over a 3‐year period.

Material and Methods: One hundred and twenty‐six subjects aged at least 20 years with a maximum of two tooth sites with probing pocket depth (PPD)>4 mm and no proximal sites with clinical attachment loss participated in the study. Primary prevention was provided at baseline of the study and then every 6 months. Plaque, bleeding on probing (BoP) and PPD were scored at baseline, 1, 2 and 3 years.

Results: There were no significant changes in the plaque score over the 3 years. After year 1, the BoP score was significantly improved with 5.6%, while no further improvement in BoP was found at years 2 and 3. The mean PPD decreased from 2.3 to 2.1 mm over the 3 years (p<0.05).

Conclusion: Although some individuals exhibiting minor signs of periodontal pathology may have benefited from the primary prevention, the overall clinical improvement was limited for such subjects in the present 3‐year study.
Does periodontal care improve glycemic control? The Department of Veterans Affairs Dental Diabetes Study
Authors: Jones Judith A. , Miller Donald R. , Wehler Carolyn J. , Rich Sharron E. , Krall‐Kaye Elizabeth A. , McCoy Linda C. , Christiansen Cindy L. , Rothendler James A. , Garcia Raul I.
Published: November 2006

Objectives: Report results of a randomized‐clinical trial of the efficacy of periodontal care in the improvement of glycemic control in 165 veterans with poorly controlled diabetes over 4 months.

Methods: Outcomes were change in Haemoglobin A1c (HbA1c) in the Early Treatment versus untreated (Usual Care) groups and percent of participants with decreases in HbA1c. Analyses included simple/multiple variable linear/logistic regressions, adjusted for baseline HbA1c, age, and duration of diabetes.

Results: Unadjusted analyses showed no differences between groups. After adjustment for baseline HbA1c, age, and diabetes duration, the mean absolute HbA1c change in the Early Treatment group was −0.65%versus−0.51% in the Usual Care group (p=0.47). Adjusted odds for improvement by 0.5% in the Early Treatment group was 1.67 (95% confidence interval: 0.84, 3.34, p=0.14). Usual Care subjects were twice as likely to increase insulin from baseline to 4 months (20%versus 11%, p=0.12) and less likely to decrease insulin (1%versus 6%, p=0.21) than Early Treatment subjects. Among insulin users at baseline, more increased insulin in the Usual Care group (40%versus 21%, p=0.06).

Conclusions: No significant benefit was found for periodontal therapy after 4 months in this study; trends in some results were in favour of periodontal treatment.
The Mythologeme of Siberia
Authors: Tiupa Valerii
Published: November 2006

This article is deals with the literary image of Siberia in nineteenth‐ and twentieth‐century Russian literature. Siberia became more than just a locale in both Russian literature and in the public consciousness: it became a particular concept, a complex idea. Traditionally associated with severe weather, long dark winters and later the proverbial place of penal servitudes, Siberia as a topos began to be unconsciously interpreted as the mythological “land of the dead.” The author analyzes a wide range of examples from texts by Ryleev, Pushkin, Nekrasov, Dostoevsky, Tolstoy, Chekhov, Erofeev and others, and illustrates that by placing their characters in Siberia, Russian writers follow the old archetypal plot of initiation. Surviving in Siberia is hence interpreted as coming back from the dead – a social, psychological or emotional rebirth.
Keats in Teignmouth
Authors: MacKenzie Clayton G.
Published: November 2006

John Keats's sojourn in Teignmouth, Devon, during the early months of 1818 has been widely acknowledged by critics but little studied. Keats visited the town because his brother Tom had gone there on medical advice. Drawing on letters and short poems from the period, the article argues that Keats constructs an idyllic view of the Devon landscape and one that is at odds with his actual experiences in that county. There are various reasons why this may be – including the possibility that his personal and professional pressures may have encouraged him to conceptualize a rural idyll that at least offered the hypothetical possibility of an escape from the darker landscapes that were shadowing his life.
Melatonin is more effective than taurine and 5‐hydroxytryptophan against hyperglycemia‐induced kidney‐cortex tubules injurya
Authors: Derlacz Rafal A. , Sliwinska Malgorzata , Piekutowska Anna , Winiarska Katarzyna , Drozak Jakub , Bryla Jadwiga
Published: November 2006

Abstract:  The antioxidative effects of melatonin (Mel), 5‐hydroxytryptophan (5‐HTP) and taurine (TAU) on hyperglycemia‐induced oxidative stress was investigated in primary cultures of kidney‐cortex tubule cells grown in metabolically and hormonally defined medium. In the presence of 30 mm glucose (hyperglycemic conditions), cell viability was decreased by about 35% in comparison with that estimated in the glucose‐depleted medium probably as a result of induction of apoptosis, as concluded from: (i) chromatin condensation and DNA fragmentation assays, (ii) a significant enhancement of reactive oxygen species (ROS) production, (iii) 8‐hydroxydeoxyguanosine (8‐OHdG) generation, (iv) an increased protein peroxidation and (v) a decline of reduced glutathione (GSH) levels leading to a disturbed glutathione redox state. The addition of 100 μm Mel to the hyperglycemic medium resulted in a twofold decrease in both 8‐OHdG accumulation and protein peroxidation as well as restoration of the control intracellular ROS levels accompanied by a substantial increase in GSH/oxidized glutathione (GSSG) ratio due to a decline in GSSG content. ROS elimination was also achieved in the presence of 1 mm TAU which diminished protein and DNA injuries by about 25% and 30%, respectively. On the contrary, the action of 100 μm 5‐HTP on ROS level, 8‐OHdG generation, protein peroxidation and GSH/GSSG ratio was negligible. Thus, in contrast to 5‐HTP and TAU, Mel might be considered as beneficial for diabetes therapy, particularly in terms of reduction of hyperglycemia‐induced kidney injury.
Review article: oesophageal function testing ‐ the old and the new
Authors: VAEZI M. F.
Published: November 2006

Gastro‐oesophageal reflux disease can manifest typically with heartburn and regurgitation and atypically with extra‐oesophageal symptoms, such as chest pain, worsening asthma, chronic cough or laryngitis.

Although acid‐suppressive therapy can help identify individuals in whom gastro‐oesophageal reflux disease is the cause of their symptoms, diagnostic testing is often needed to evaluate those with persistent symptoms.

Recent advances in oesophageal diagnostic testing include the advent of a wireless pH‐monitoring device that eliminates the need for a transnasal catheter as well as an ambulatory impedance monitoring device that allows measurement of weakly acidic or non‐acidic refluxate.

The advantages and disadvantages as well as clinical utility of these new, as well as traditional, oesophageal‐measuring devices are discussed in this review.
Drawing the Boundaries of Nanoscience — Rationalizing the Concerns?
Authors: Kaiser Mario
Published: November 2006

Imagine your body is populated by billions of respirocytes capable of delivering 236 times more oxygen than your natural red blood cells. These mechanical, micron sized spheres are appropriately programmed by your physician to meet your personal requirements, be it the treatment of anemia or the enhancement of your physical abilities. Robert Freitas’ vision of such artificial blood cells comprised of nanometer-scale components was published in 1998 in a peer-reviewed medical journal, and was the first medical nanorobot design paper to be published.

The fact that this proposal for a future blood substitute was accepted as worthy of publication in a scientific journal, despite the inventor's explicit statement that such a device could not be built at the time, clouds the criteria upon which an informed opinion about the feasibility of such devices could be formed. In that respect, the idea of respirocytes formidably testifies to the current “blurring of fact and fiction” occurring in the field of nanotechnology.
Offense-Defense Aspects of Nanotechnologies: A Forecast of Potential Military Applications
Authors: Shipbaugh Calvin
Published: November 2006

There is growing recognition of the need to understand societal impacts of nanotechnology. Global interest in nanotechnology implies many nations will see a need to seek out advantages for military use. Militarization will inevitably include consideration of both offensive and defensive goals. This presents emerging implications for military forces in the near future, and will greatly influence the nature of warfare and peacekeeping in the distant future. The development of nanotechnology creates possibilities for both beneficial opportunities and adverse consequences as a result of application to the military strategies of both large and small nations.

The promise of nanotechnology for military and security roles derives from several innate characteristics. For example, further improvements in sensors are expected and already there are numerous reports of successful developments in research and development. Material properties can be tailored on a fine scale through nanomachining, scanning force microscopy, molecular self-assembly, and other techniques.
Is the Tobacco Settlement Constitutional?
Authors: Rajkumar Rahul , Gross Cary P. , Forman Howard P.
Published: November 2006

In August 2005, the Competitive Enterprise Institute (CEI), a conservative “think tank” and advocacy organization, filed a lawsuit in the Federal District Court for the Western District of Louisiana against the Louisiana Attorney General challenging the legality of the 1998 Master Settlement Agreement (MSA). If successful, this lawsuit could lead to the unraveling of one of the most significant opportunities to improve public health in United States history.

Under the MSA, forty-six states agreed to end their litigation against the four largest tobacco companies in the United States, who in turn agreed to pay the states an estimated $206 billion. The CEI alleges that the MSA is unconstitutional. Specifically, the suit alleges that the MSA established a cartel under which the states receive monetary payments and the four major tobacco companies are insulated from price competition – and that this arrangement violates the Compact Clause of the U.S. Constitution.
Heterozygote Carrier Testing in High Schools Abroad: What are the Lessons for the U.S.?
Authors: Ross Lainie Friedman
Published: November 2006

To promote informed reproductive decisions, prenatal carrier testing is offered to women and couples to provide information about the risk of having a child with one or more genetic conditions. Tay Sachs Disease (TSD) was one of the first conditions for which prenatal carrier testing was developed. Today, many additional conditions can be tested for, depending on prospective parental interest, family history, or ethnicity. Interestingly, most individuals and couples do not request prenatal carrier information prior to conception, and carrier testing early in gestation allows only a narrow set of reproductive options. Programs have been designed to increase preconception testing, with variable success. One of the more successful attempts to increase preconception carrier testing uptake internationally has been to offer it to adolescents in high schools.
The Balm of Gilead: Is the Provision of Treatment to Those Who Seroconvert in HIV Prevention Trials a Matter of Moral Obligation or Moral Negotiation?
Authors: Weijer Charles , LeBlanc Guy J.
Published: November 2006

Is there no balm in Gilead; is there no physician there? Why then is not the health of the daughter of my people recovered?

(Jeremiah 8:22)

In July of 2004, Cambodian sex workers staged a protest of an HIV prevention trial set to enroll 900 sex workers in Phnom Penh, charging the study planners with exploitation. The Cambodian study was one of a series of international clinical trials sponsored by the U.S. National Institutes of Health (NIH), U.S. Centers for Disease Control and Prevention (CDC), and the Bill and Melinda Gates Foundation (Gates Foundation) testing the safety and efficacy of tenofovir (Viread), an antiretroviral drug produced by Gilead Sciences, Inc., to prevent HIV transmission. To date, two of these international studies have been closed and one is suspended, prompting calls for re-examination of the ethics of HIV prevention trials.
Reviews in Medical Ethics
Authors: Blazina David , Willoughby Erin , Wilson Robin Fretwell
Published: November 2006

In his deliciously funny book, Medicare Meets Mephistopheles, Professor David Hyman argues that Medicare corrupts our most base impulses. It urges us, for example, to grab for more than our fair share of benefits while offering providers “the prospect of staggering amounts of money – even as…actuaries were promising Congress that the Medicare program would be easily affordable.” Modeled on C.S. Lewis’ The Screwtape Letters, Professor Hyman's satirical examination of Medicare takes the form of a memo to Satan from an underling demon in the Department of Illness and Satanic Services (DISS), reporting on the success of Satan's diabolical plot to corrupt humanity. Sprinkled with political cartoons, absurd (but true) stories of Medicare's over-the-top fraud enforcement efforts, and a historical account of Medicare's genesis (replete with Congressmen and strippers), Medicare Meets Mephistopheles gives us a well-researched and easy-to-read primer on the biggest pot of gold in medicine.
Physiological basis for a causal relationship of obstructive sleep apnoea to hypertension
Authors: Weiss J. Woodrow , Liu M. D. Yuzhen , Huang Jianhua
Published: November 2006

Obstructive sleep apnoea (OSA) is causally related to systemic hypertension through sustained sympathoexcitation. The causes of this sympathoexcitation remain uncertain; however, substantial animal and human data suggest that cyclic intermittent hypoxia (CIH), as is experienced at night by patients with OSA, provides the causal link between upper airway obstruction during sleep and sympathetic activation during waking. Direct and indirect evidence indicates that CIH leads to sympathoexcitation by two mechanisms: (1) augmentation of peripheral chemoreflex sensitivity (hypoxic acclimatization); and (2) direct effects on sites of central sympathetic regulation, such as the subfornical organ and the paraventricular nucleus of the hypothalamus. Initial reports suggest that the molecular mechanisms influencing peripheral chemoreflex sensitivity and central sympathetic activity may be the same, involving such neuromodulators as angiotensin II, endothelin and nitric oxide.
High CO2 chemosensitivity versus wide sensing spectrum: a paradoxical problem and its solutions in cultured brainstem neurons
Authors: Su Junda , Yang Liang , Zhang Xiaoli , Rojas Asheebo , Shi Yun , Jiang Chun
Published: November 2006

CO2 central chemoreceptors play an important role in cardiorespiratory control. They are highly sensitive to PCO2 in a broad range. These two sensing properties seem paradoxical as none of the known pH‐sensing molecules can achieve both. Here we show that cultured neuronal networks are likely to solve the sensitivity versus spectrum problem with parallel and serial processes. Studies were performed on dissociated brainstem neurons cultured on microelectrode arrays. Recordings started after a 3 week initial period of culture. A group of neurons were dose‐dependently stimulated by elevated CO2 with a linear response ranging from 20 to 70 Torr. The firing rate of some neurons increased by up to 30% in response to a 1 Torr PCO2 change, indicating that cultured brainstem neuronal networks retain high CO2 sensitivity in a broad range. Inhibition of Kir channels selectively suppressed neuronal responses to hypocapnia and mild hypercapnia. Blockade of TASK channels affected neuronal response to more severe hypercapnia. These were consistent with the pKa values measured for these K+ channels in a heterologous expression system. The CO2 chemosensitivity was reduced but not eliminated by blockade of presynaptic input from serotonin, substance P or glutamate neurons, indicating that both pre and postsynaptic neurons contribute to the CO2 chemosensitivity. These results therefore strongly suggest that the physiological PCO2 range appears to be covered by multiple sensing molecules, and that the high sensitivity may be achieved by cellular mechanisms via synaptic amplification in cultured brainstem neurons.
Intrauterine growth restriction delays cardiomyocyte maturation and alters coronary artery function in the fetal sheep
Authors: Bubb Kristen J. , Cock Megan L. , Black M. Jane , Dodic Miodrag , Boon Wee‐Ming , Parkington Helena C. , Harding Richard , Tare Marianne
Published: November 2006

There is now extensive evidence suggesting that intrauterine perturbations are linked with an increased risk of developing cardiovascular disease. Human epidemiological studies, supported by animal models, have demonstrated an association between low birth weight, a marker of intrauterine growth restriction (IUGR), and adult cardiovascular disease. However, little is known of the early influence of IUGR on the fetal heart and vessels. The aim of this study was to determine the effects of late gestational IUGR on coronary artery function and cardiomyocyte maturation in the fetus. IUGR was induced by placental embolization in fetal sheep from 110 to 130 days of pregnancy (D110–130); term ∼D147; control fetuses received saline. At necropsy (D130), wire and pressure myography was used to test endothelial and smooth muscle function, and passive mechanical wall properties, respectively, in small branches of left descending coronary arteries. Myocardium was dissociated for histological analysis of cardiomyocytes. At D130, IUGR fetuses (2.7 ± 0.1 kg) were 28% lighter than controls (3.7 ± 0.3 kg; P= 0.02). Coronary arteries from IUGR fetuses had enhanced responsiveness to the vasoconstrictors, angiotensin II and the thromboxane analogue U46619, than controls (P < 0.01). Endothelium‐dependent and ‐independent relaxations were not different between groups. Coronary arteries of IUGR fetuses were more compliant (P= 0.02) than those of controls. The incidence of cardiomyocyte binucleation was lower in the left ventricles of IUGR fetuses (P= 0.02), suggestive of retarded cardiomyocyte maturation. We conclude that late gestational IUGR alters the reactivity and mechanical wall properties of coronary arteries and cardiomyocyte maturation in fetal sheep, which could have lifelong implications for cardiovascular function.
Pinch‐current injection defines two discharge profiles in mouse superficial dorsal horn neurones, in vitro
Authors: Graham B. A. , Brichta A. M. , Callister R. J.
Published: November 2006

Neurones in the superficial dorsal horn (SDH) are a major target for nociceptive afferents and play an important role in pain processing. One approach to understanding the role of SDH neurones has been to study their action potential (AP) discharge in spinal cord slices during injection of depolarizing step‐currents. Four or five neurone subpopulations are typically identified based on AP discharge, with various roles proposed for each in pain processing. During noxious peripheral stimulation in vivo, however, SDH neurones are activated via synaptic inputs. This produces a conductance change with different somato‐dendritic distributions and temporal characteristics to that provided by a somatic step‐current injection. Here we introduce an alternative approach to studying SDH neurone discharge under in vitro conditions. We recorded voltage‐clamp responses in SDH neurones, in vivo, during noxious mechanical stimulation of the hindpaw (1 s pinch, ∼100 g mm−2). From these recordings a representative ‘pinch‐current’ was selected and subsequently injected into SDH neurones in spinal cord slices (recording temperature 32°C). Pinch‐current‐evoked discharge was compared to that evoked by rectangular step‐current injections. Pinch‐ and step‐current‐evoked AP discharge frequency was highly correlated (r2= 0.61). This was also true for rheobase current comparisons (r2= 0.61). Conversely, latency to discharge and discharge duration were not correlated when step‐ and pinch‐current responses were compared. When neurones were grouped according to step‐current‐evoked discharge, five distinct patterns were apparent (tonic firing, initial bursting, delayed firing, single spiking, and reluctant firing). In contrast, pinch‐current responses separated into two clear patterns of activity (robust and resistant firing). During pinch‐current injection, tonic‐firing and initial‐bursting neurones exhibited robust AP discharge with similar characteristics. In contrast, single‐spiking and reluctant‐firing neurones were resistant to AP discharge. Delayed‐firing neurones exhibited pinch‐current responses that were transitional between those of tonic‐firing/initial‐bursting and single‐spiking/reluctant‐firing neurones. Injection of digitally filtered pinch‐currents indicated that transient current fluctuations are necessary for robust repetitive discharge in initial‐bursting neurones. These data suggest the functional significance of the diverse step‐current‐evoked firing patterns, previously reported in SDH neurones remains to be fully understood. When a ‘facsimile’ current profile or pinch‐current is used in place of step‐currents, AP discharge diversity is much reduced.
Comment on Papers by Chong
et al
., Nishio
et al
., and Suri
et al
. on Diabetes Reversal in NOD Mice
Authors: Faustman Denise L. , Tran Simon D. , Kodama Shohta , Lodde Beatrijs M. , Szalayova Ildiko , Key Sharon , Toth Zsuzsanna E. , Mezey Éva
Published: November 2006

Chong
et al
., Nishio
et al
., and Suri
et al
. (Reports, 24 March 2006, pp.
1774
,
1775
, and
1778
) confirmed that treating nonobese diabetic (NOD) mice with an immune adjuvant and semisyngenic spleen cells can reverse the disease but found that spleen cells did not contribute to the observed recovery of pancreatic islets. We show that islet regeneration predominately originates from endogenous cells but that introduced spleen cells can also contribute to islet recovery.
Response to Comment on Nishio
et al
. on Diabetes Reversal in NOD Mice
Authors: Nishio Junko , Gaglia Jason L. , Turvey Stuart E. , Campbell Christopher , Benoist Christophe , Mathis Diane
Published: November 2006

Contrary to previous findings, we found no significant differentiation of splenocytes into pancreatic islet cells in nonobese diabetic (NOD) mice treated with an immune adjuvant and allogenic spleen cells. We show that our single-nucleotide polymorphism assay has the requisite sensitivity to support our contention. The experiments of Faustman
et al
. lack adequate controls, and we maintain that no evidence of islet regeneration has been presented.
Distinct Populations of Primary and Secondary Effectors During RNAi in
C. elegans
Authors: Pak Julia , Fire Andrew
Published: November 2006

RNA interference (RNAi) is a phylogenetically widespread gene-silencing process triggered by double-stranded RNA. In plants and
Caenorhabditis elegans
, two distinct populations of small RNAs have been proposed to participate in RNAi: “Primary siRNAs” (derived from DICER nuclease-mediated cleavage of the original trigger) and “secondary siRNAs” [additional small RNAs whose synthesis requires an RNA-directed RNA polymerase (RdRP)]. Analyzing small RNAs associated with ongoing RNAi in
C. elegans
, we found that secondary siRNAs constitute the vast majority. The bulk of secondary siRNAs exhibited structure and sequence indicative of a biosynthetic mode whereby each molecule derives from an independent de novo initiation by RdRP. Analysis of endogenous small RNAs indicated that a fraction derive from a biosynthetic mechanism that is similar to that of secondary siRNAs formed during RNAi, suggesting that small antisense transcripts derived from cellular messenger RNAs by RdRP activity may have key roles in cellular regulation.
A Sea-Floor Spreading Event Captured by Seismometers
Authors: Tolstoy M. , Cowen J. P. , Baker E. T. , Fornari D. J. , Rubin K. H. , Shank T. M. , Waldhauser F. , Bohnenstiehl D. R. , Forsyth D. W. , Holmes R. C. , Love B. , Perfit M. R. , Weekly R. T. , Soule S. A. , Glazer B.
Published: November 2006

Two-thirds of Earth's surface is formed at mid-ocean ridges, yet sea-floor spreading events are poorly understood because they occur far beneath the ocean surface. At 9°50'N on the East Pacific Rise, ocean-bottom seismometers recently recorded the microearthquake character of a mid-ocean ridge eruption, including precursory activity. A gradual ramp-up in activity rates since seismic monitoring began at this site in October 2003 suggests that eruptions may be forecast in the fast-spreading environment. The pattern culminates in an intense but brief (∼6-hour) inferred diking event on 22 January 2006, followed by rapid tapering to markedly decreased levels of seismicity.
Homolactate Fermentation by Metabolically Engineered
Escherichia coli
Strains
Authors: Zhu Y. , Eiteman M. A. , DeWitt K. , Altman E.
Published: November 2006

We report the homofermentative production of lactate in
Escherichia coli
strains containing mutations in the
aceEF
,
pfl
,
poxB
, and
pps
genes, which encode the pyruvate dehydrogenase complex, pyruvate formate lyase, pyruvate oxidase, and phosphoenolpyruvate synthase, respectively. The process uses a defined medium and two distinct fermentation phases: aerobic growth to an optical density of about 30, followed by nongrowth, anaerobic production. Strain YYC202 (
aceEF pfl poxB pps
) generated 90 g/liter lactate in 16 h during the anaerobic phase (with a yield of 0.95 g/g and a productivity of 5.6 g/liter · h). Ca(OH)
2
was found to be superior to NaOH for pH control, and interestingly, significant succinate also accumulated (over 7 g/liter) despite the use of N
2
for maintaining anaerobic conditions. Strain ALS961 (YYC202
ppc
) prevented succinate accumulation, but growth was very poor. Strain ALS974 (YYC202
frdABCD
) reduced succinate formation by 70% to less than 3 g/liter.
13
C nuclear magnetic resonance analysis using uniformly labeled acetate demonstrated that succinate formation by ALS974 was biochemically derived from acetate in the medium. The absence of uniformly labeled succinate, however, demonstrated that glyoxylate did not reenter the tricarboxylic acid cycle via oxaloacetate. By minimizing the residual acetate at the time that the production phase commenced, the process with ALS974 achieved 138 g/liter lactate (1.55 M, 97% of the carbon products), with a yield of 0.99 g/g and a productivity of 6.3 g/liter · h during the anaerobic phase.
Comparison of Primer Sets for Use in Automated Ribosomal Intergenic Spacer Analysis of Aquatic Bacterial Communities: an Ecological Perspective
Authors: Jones Stuart E. , Shade Ashley L. , McMahon Katherine D. , Kent Angela D.
Published: November 2006

Two primer sets for automated ribosomal intergenic spacer analysis (ARISA) were used to assess the bacterial community composition (BCC) in Lake Mendota, Wisconsin, over 3 years. Correspondence analysis revealed differences in community profiles generated by different primer sets, but overall ecological patterns were conserved in each case. ARISA is a powerful tool for evaluating BCC change through space and time, regardless of the specific primer set used.
Construction of a
Vibrio splendidus
Mutant Lacking the Metalloprotease Gene
vsm
by Use of a Novel Counterselectable Suicide Vector
Authors: Le Roux Frédérique , Binesse Johan , Saulnier Denis , Mazel Didier
Published: November 2006

Vibrio splendidus
is a dominant culturable
Vibrio
in seawater, and strains related to this species are also associated with mortality in a variety of marine animals. The determinants encoding the pathogenic properties of these strains are still poorly understood; however, the recent sequencing of the genome of
V. splendidus
LGP32, an oyster pathogen, provides an opportunity to decipher the basis of the virulence properties by disruption of candidate genes. We developed a novel suicide vector based on the
pir
-dependent R6K replicative origin, which potentially can be transferred by RP4-based conjugation to any
Vibrio
strain and which also carries the plasmid F toxin
ccdB
gene under control of the P

BAD

promoter. We demonstrated that this genetic system allows efficient counterselection of integrated plasmids in the presence of arabinose in both
V. splendidus
and
Vibrio cholerae
and thus permits efficient markerless allelic replacement in these species. We used this technique to construct several mutants of
V. splendidus
LGP32, including a derivative with a secreted metalloprotease gene,
vsm
, deleted. We found that this gene is essential for LGP32 extracellular product toxicity when the extracellular products are injected into oysters but is not necessary for virulence of bacteria in the oyster infection model when bacteria are injected.
Performance of a Commercial Immunoglobulin M Antibody Capture Assay Using Analyte-Specific Reagents To Screen for Interfering Factors during a West Nile Virus Epidemic Season in Nebraska
Authors: Sambol Anthony R. , Hinrichs Steven H. , Hogrefe Wayne R. , Schweitzer Beth K.
Published: November 2006

In 2003, the Nebraska Public Health Laboratory tested more than 10,371 serum and 516 cerebral spinal fluid specimens. Results showed that without performing the interfering factors screen for specimens in the low positive index value range of >1.1 to ≤3.5, a false positivity rate of 6.5% would have been realized.
Regulation of
Vibrio
Polysaccharide Synthesis and Virulence Factor Production by CdgC, a GGDEF-EAL Domain Protein, in
Vibrio cholerae
Authors: Lim Bentley , Beyhan Sinem , Yildiz Fitnat H.
Published: November 2006

In
Vibrio cholerae
, the second messenger
3′,5′-cyclic diguanylic acid (c-di-GMP) regulates
several cellular processes, such as formation of corrugated colony
morphology, biofilm formation, motility, and virulence factor
production. Both synthesis and degradation of c-di-GMP in the cell are
modulated by proteins containing GGDEF and/or EAL domains, which
function as a diguanylate cyclase and a phosphodiesterase,
respectively. The expression of two genes,
cdgC
and
mbaA
, which encode proteins harboring both GGDEF and EAL
domains is higher in the rugose phase variant of
V. cholerae
than in the smooth variant. In this study, we carried out gene
expression analysis to determine the genes regulated by CdgC in the
rugose and smooth phase variants of
V. cholerae
. We determined
that CdgC regulates expression of genes required for
V.
cholerae
polysaccharide synthesis and of the transcriptional
regulator genes
vpsR
,
vpsT
, and
hapR
. CdgC
also regulates expression of genes involved in extracellular protein
secretion, flagellar biosynthesis, and virulence factor production. We
then compared the genes regulated by CdgC and by MbaA, during both
exponential and stationary phases of growth, to elucidate processes
regulated by them. Identification of the regulons of CdgC and MbaA
revealed that the regulons overlap, but the timing of regulation
exerted by CdgC and MbaA is different, suggesting the interplay and
complexity of the c-di-GMP signal transduction pathways operating in
V.
cholerae
.
Lateral Gene Transfer In Vitro in the Intracellular PathogenChlamydia trachomatis
Authors: DeMars Robert , Weinfurter Jason , Guex Erin , Lin John , Potucek Yvonne
Published: November 2006

Genetic recombinants that resulted from lateral gene transfer (LGT) have been detected in sexually transmitted disease isolates ofChlamydia trachomatis, but a mechanism for LGT inC. trachomatishas not been described. We describe here a system that readily detectsC. trachomatisLGT in vitro and that may facilitate discovery of its mechanisms. Host cells were simultaneously infected in the absence of antibiotics with an ofloxacin-resistant mutant and a second mutant that was resistant to lincomycin, trimethoprim, or rifampin. Selection for doubly resistantC. trachomatisisolates in the progeny detected apparent recombinant frequencies of 10−4to 10−3, ∼104times more frequent than doubly resistant spontaneous mutants in progeny from uniparental control infections. Polyclonal doubly resistant populations and clones isolated from them in the absence of antibiotics had the specific resistance-conferring mutations present in the parental mutants; absence of the corresponding normal nucleotides indicated that they had been replaced by homologous recombination. These results eliminate spontaneous mutation, between-strain complementation, and heterotypic resistance as general explanations of multiply resistantC. trachomatisthat originated in mixed infections in our experiments and demonstrate genetic stability of the recombinants. The kind of LGT we observed might be useful for creating new strains for functional studies by creating new alleles or combinations of alleles of polymorphic loci and might also disseminate antibiotic resistance genes in vivo. The apparent absence of phages and conjugative plasmids inC. trachomatissuggests that the LGT may have occurred by means of natural DNA transformation. Therefore, the experimental system may have implications for genetically alteringC. trachomatisby means of DNA transfer.
Integration and Excision of a Newly DiscoveredBacteroidesConjugative Transposon, CTnBST
Authors: Wesslund Neil A. , Wang Gui-Rong , Song Bo , Shoemaker Nadja B. , Salyers Abigail A.
Published: November 2006

Conjugative transposons (CTns) are major contributors to the spread of antibiotic resistance genes amongBacteroidesspecies. CTnBST, a newly discoveredBacteroidesconjugative transposon, carries an erythromycin resistance gene,ermB, and previously has been estimated to be about 100 kbp in size. We report here the locations and sequencing of both of its ends. We have also located and sequenced the gene that catalyzes the integration of CTnBST,intBST. The integrase gene encodes a 377-amino-acid protein that has the C-terminal R-K-H-R-H-Y motif that is characteristic of members of the tyrosine recombinase family of integrases. DNA sequence comparisons of the ends of CTnBST, the joined ends of the circular intermediate, and the preferred site into which the circular form of CTnBST had integrated revealed that the preferred integration site (attB1) contained an 18-bp sequence of identity to the crossover region,attBST, on CTnBST. Although this site was used in about one-half of the integration events, sequence analysis of these integration events revealed that both CTnBST and a miniature form of CTnBST (miniBST) integrated into a variety of other sites in the chromosome. All of the sites had two conserved regions, AATCTG and AAAT. These two regions flanked a 2-bp sequence, bp 10 and bp 11 of the 18-bp sequence, that varied in some of the different sites and sometimes in theattBSTsequences. Our results suggest that CTnBST integrates site selectively and that the crossover appears to occur within a 12-bp region that contains the two regions of conserved sequences.