bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colour and pattern selectivity of receptive fields in superior colliculus of marmoset monkeys
Authors: Tailby Chris , Cheong Soon Keen , Pietersen Alexander N. , Solomon Samuel G. , Martin Paul R. 
Published: June 2012

Key points
In addition to supplying signals for conscious visual perception, the pathways from eye to brain serve visual functions such as reflex eye movements, which are controlled by a brain area called the superior colliculus (SC).
It is known that short‐wavelength sensitive (S or ‘blue’) cone photoreceptors serve an evolutionary ancient pathway for colour vision but whether S cones also contribute to reflex eye movements is poorly understood.
We show that in recordings from anaesthetised marmoset monkeys, S cones do not contribute to visual responses in the SC. Thus, although S cones are a primitive part of the visual system their signals are selectively directed to thalamo‐cortical pathways serving colour vision.
The result also implies that colour‐selective responses reported in SC of awake monkeys must arrive through indirect (non‐retinal) inputs to the SC.
Abstract  The main subcortical visual targets of retinal output neurones (ganglion cells) are the parvocellular and magnocellular layers of the dorsal lateral geniculate nucleus (LGN) in the thalamus. In addition, a small and heterogeneous collection of ganglion cell axons projects to the koniocellular layers of the LGN, to the superior colliculus (SC), and to other subcortical targets. The functional (receptive field) properties and target specificity of these non‐parvocellular, non‐magnocellular populations remain poorly understood. It is known that one population of koniocellular layer cells in the LGN (blue‐On cells) receives dominant functional input from short‐wavelength sensitive (S or ‘blue’) cones. Here we asked whether SC neurones also receive S cone inputs. We made extracellular recordings from single neurones (n= 38) in the SC of anaesthetised marmoset monkeys. Responses to drifting and flashed gratings providing defined levels of cone contrast were measured. The SC receptive fields we recorded were often binocular, showed ‘complex cell’ like responses (On–Off responses), strong bandpass spatial frequency tuning, direction selectivity, and many showed strong and rapid habituation to repeatedly presented stimuli. We found no evidence for dominant S cone input to any SC neurone recorded. These data suggest that S cone signals may reach cortical pathways for colour vision exclusively through the koniocellular division of the lateral geniculate nucleus.
Dietary nitrate increases tetanic [Ca2+]i and contractile force in mouse fast‐twitch muscle
Authors: Hernández Andrés , Schiffer Tomas A. , Ivarsson Niklas , Cheng Arthur J. , Bruton Joseph D. , Lundberg Jon O. , Weitzberg Eddie , Westerblad Håkan 
Published: June 2012

Key points
Dietary supplementation with inorganic nitrate has beneficial effects on skeletal muscle responses to exercise.
Both mitochondrial and extra‐mitochondrial explanations have been proposed.
Contractile force of fast‐twitch muscles was enhanced in mice supplemented with 1 mm NaNO3 in drinking water for 7 days.
Myoplasmic free [Ca2+] during tetanic stimulation was increased in fast‐twitch muscles of nitrate‐supplemented mice and this was accompanied by increased expression of calsequestrin 1 and the dihydropyridine receptor.
These results provide a new mechanism by which nitrate exerts beneficial effects on muscle function with applications to sports performance and a potential therapeutic role in conditions with muscle weakness.
Abstract  Dietary inorganic nitrate has profound effects on health and physiological responses to exercise. Here, we examined if nitrate, in doses readily achievable via a normal diet, could improve Ca2+ handling and contractile function using fast‐ and slow‐twitch skeletal muscles from C57bl/6 male mice given 1 mm sodium nitrate in water for 7 days. Age matched controls were provided water without added nitrate. In fast‐twitch muscle fibres dissected from nitrate treated mice, myoplasmic free [Ca2+] was significantly greater than in Control fibres at stimulation frequencies from 20 to 150 Hz, which resulted in a major increase in contractile force at ≤50 Hz. At 100 Hz stimulation, the rate of force development was ∼35% faster in the nitrate group. These changes in nitrate treated mice were accompanied by increased expression of the Ca2+ handling proteins calsequestrin 1 and the dihydropyridine receptor. No changes in force or calsequestrin 1 and dihydropyridine receptor expression were measured in slow‐twitch muscles. In conclusion, these results show a striking effect of nitrate supplementation on intracellular Ca2+ handling in fast‐twitch muscle resulting in increased force production. A new mechanism is revealed by which nitrate can exert effects on muscle function with applications to performance and a potential therapeutic role in conditions with muscle weakness.
Vancomycin Tolerance in Methicillin-Resistant Staphylococcus aureus: Influence of Vancomycin, Daptomycin, and Telavancin on Differential Resistance Gene Expression
Authors: Rose Warren E. , Fallon Michael , Moran John J. M. , Vanderloo Joshua P. 
Published: June 2012

ABSTRACT

Methicillin-resistant
Staphylococcus aureus
(MRSA) isolates that are susceptible to vancomycin but are tolerant to its killing effect may present a potential challenge for effective treatment. This study compared the microbiologic characteristics of clinical vancomycin-tolerant (VT-MRSA) and vancomycin-susceptible (VS-MRSA) strains using phenotypic and gene regulation studies. MRSA isolates collected from vancomycin-treated patients with bacteremia over a 5-year period were analyzed for vancomycin, daptomycin, and telavancin susceptibility, as well as accessory gene regulator (
agr
) group and function. Vancomycin tolerance was defined by a minimum bactericidal concentration (MBC)/minimum inhibitor concentration (MIC) ratio of ≥32 mg/liter. VT-MRSA isolates were compared to VS-MRSA isolates for differences in antimicrobial susceptibility, time-kill activity, and gene expression of key cell envelope response genes
vraSR
,
dltA
, and
mprF
. All 115 isolates evaluated were susceptible to vancomycin, daptomycin, and telavancin. Seven isolates (6%) were VT-MRSA.
agr
group II was more prevalent in isolates with vancomycin MBC/MIC ratios of ≥8. In time-kill analyses, VT-MRSA had reduced vancomycin killing, but daptomycin and telavancin activities were maintained. Significantly greater gene expression was observed in VT-MRSA after 72 h of subinhibitory antibiotic exposures. Vancomycin most notably increased
vraSR
expression (
P
= 0.002 versus VS-MRSA strains). Daptomycin and telavancin increased expression of all genes studied, most significantly
mprF
expression (
P
< 0.001). Longer durations of antibiotic exposure (72 h versus 24 h) resulted in substantial increases in gene expression in VT-MRSA. Although the clinical impact of VT-MRSA is not fully recognized, these data suggest that VT-MRSA strains, while still susceptible, have altered gene regulation to adapt to the antimicrobial effects of glyco- and lipopeptides that may emerge during prolonged durations of exposure.
Campylobacter jejuni-Mediated Induction of CC and CXC Chemokines and Chemokine Receptors in Human Dendritic Cells
Authors: Hu Lan , Bray Mechelle D. , Geng Yansheng , Kopecko Dennis J. 
Published: June 2012

ABSTRACT

Campylobacter jejuni
is a leading worldwide bacterial cause of human diarrheal disease. Although the specific molecular mechanisms of
C. jejuni
pathogenesis have not been characterized in detail, host inflammatory responses are thought to be major contributing factors to the resulting typical acute colitis. The intestinal mucosal chemokine response is particularly important in the initial stages of bacterium-induced gut inflammation. Chemokines attract blood phagocytes and lymphocytes to the site of infection and regulate immune cell maturation and the development of localized lymphoid tissues. The production of chemokines by dendritic cells (DCs) following
Campylobacter
infection has not yet been analyzed. In the current study, we infected human monocyte-derived DCs with
C. jejuni
to examine the production of key proinflammatory chemokines and chemokine receptors. The chemokines, including CC families (macrophage inflammatory protein 1α [MIP-1α], MIP-1β, RANTES) and CXC families (growth-related oncogene α [GRO-α], IP-10, and monokine induced by gamma interferon [MIG]), were upregulated in
Campylobacter
-infected DCs. Chemokine receptors CCR6 and CCR7, with roles in DC trafficking, were also induced in
Campylobacter
-infected DCs. Further,
Campylobacter
infection stimulated the phosphorylation of P38, P44/42, and stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK) mitogen-activated protein kinases (MAPKs) in DCs. NF-κB activation was specifically involved in chemokine induction in DCs infected with
C. jejuni
. Additionally, STAT3 was significantly increased in
Campylobacter
-infected DCs compared to that in uninfected DCs. These results suggest that DCs play a significant role in the initiation and modulation of the inflammatory response by enlisting monocytes, neutrophils, and T lymphocytes during human intestinal infection with
Campylobacter
.
Complexity Theory for Operators in Analysis
Authors: Kawamura Akitoshi , Cook Stephen 
Published: June 2012

We propose an extension of the framework for discussing the computational complexity of problems involving uncountably many objects, such as real numbers, sets and functions, that can be represented only through approximation. The key idea is to use a certain class of string functions as names representing these objects. These are more expressive than infinite sequences, which served as names in prior work that formulated complexity in more restricted settings. An advantage of using string functions is that we can define their size in a way inspired by higher-type complexity theory. This enables us to talk about computation on string functions whose time or space is bounded polynomially in the input size, giving rise to more general analogues of the classes P, NP, and PSPACE. We also define NP- and PSPACE-completeness under suitable many-one reductions.
Because our framework separates machine computation and semantics, it can be applied to problems on sets of interest in analysis once we specify a suitable representation (encoding). As prototype applications, we consider the complexity of functions (operators) on real numbers, real sets, and real functions. For example, the task of numerical algorithms for solving a certain class of differential equations is naturally viewed as an operator taking real functions to real functions. As there was no complexity theory for operators, previous results only stated how complex the solution can be. We now reformulate them and show that the operator itself is polynomial-space complete.
Diagnostic efficiency of troponin T measurements in acute myocardial infarction.
Authors: Katus H A , Remppis A , Neumann F J , Scheffold T , Diederich K W , Vinar G , Noe A , Matern G , Kuebler W 
Published: June 2012

BACKGROUND
The present study was designed to evaluate the efficiency of a newly developed troponin T enzyme immunoassay for the detection of acute myocardial infarction.

METHODS AND RESULTS
The study comprised 388 patients admitted with chest pain and suspected myocardial infarction and 101 patients with skeletal muscle damage and additional suspected myocardial cell damage. Troponin T was elevated to more than twice the analytical sensitivity of the assay (0.5 microgram/l) in all patients with non-Q wave (range, 1.2-5 micrograms/l) and Q wave infarction (range, 3-220 micrograms/l). Troponin T appeared in serum as early as 3 hours after onset of pain in 50% of the patients and remained elevated in all patients for more than 130 hours, revealing release kinetics of both free cytosolic and structurally bound molecules. The diagnostic efficiency of troponin T was superior to that of creatine kinase-MB (98% versus 97%) and remained at 98% until 5.5 days after admission, if patients with unstable angina were excluded from analysis. In the 79 patients with unstable angina, troponin T was elevated (range, 0.55-3.1 micrograms/l) in at least one blood sample from each of 37 patients (56%). Circulating troponin T was correlated to the presence of reversible ST segment or T wave changes on the electrocardiogram (p less than 0.005) and to the frequency of in-hospital complications. In the 101 patients with skeletal muscle damage and suspected additional cardiac muscle damage, troponin T was the most useful test; its efficiency was 89% or 94% (depending on the discriminator value used) as compared with 63% for creatine kinase-MB.

CONCLUSIONS
Thus, the data of the study indicate that the newly developed troponin T test improves the efficiency of serodiagnostic tools for the detection of myocardial cell necrosis as compared with conventionally used cardiac enzymes.
Intravascular ultrasound imaging of human coronary arteries in vivo. Analysis of tissue characterizations with comparison to in vitro histological specimens.
Authors: Tobis J M , Mallery J , Mahon D , Lehmann K , Zalesky P , Griffith J , Gessert J , Moriuchi M , McRae M , Dwyer M L 
Published: June 2012

BACKGROUND
Intravascular ultrasound imaging was performed in 27 patients after coronary balloon angioplasty to quantify the lumen and atheroma cross-sectional areas.

METHODS AND RESULTS
A 20-MHz ultrasound catheter was inserted through a 1.6-mm plastic introducer sheath across the dilated area to obtain real-time images at 30 times/sec. The ultrasound images distinguished the lumen from atheroma, calcification, and the muscular media. The presence of dissection between the media and the atheroma was well visualized. These observations of tissue characterization were compared with an in vitro study of 20 human atherosclerotic artery segments that correlated the ultrasound images to histological preparations. The results indicate that high-quality intravascular ultrasound images under controlled in vitro conditions can provide accurate microanatomic information about the histological characteristics of atherosclerotic plaques. Similar quality cross-sectional ultrasound images were also obtained in human coronary arteries in vivo. Quantitative analysis of the ultrasound images from the clinical studies revealed that the mean cross-sectional lumen area after balloon angioplasty was 5.0 +/- 2.0 mm2. The mean residual atheroma area at the level of the prior dilatation was 8.7 +/- 3.4 mm2, which corresponded to 63% of the available arterial cross-sectional area. At the segments of the coronary artery that appeared angiographically normal, the ultrasound images demonstrated the presence of atheroma involving 4.7 +/- 3.2 mm2, which was a mean of 35 +/- 23% of the available area bounded by the media.

CONCLUSIONS
Intravascular ultrasound appears to be more sensitive than angiography for demonstrating the presence and extent of atherosclerosis and arterial calcification. Intracoronary imaging after balloon angioplasty reveals that a significant amount of atheroma is still present, which may partly explain why the incidence of restenosis is high after percutaneous transluminal coronary angioplasty.
Evidence for structural sympathetic reinnervation after orthotopic cardiac transplantation in humans.
Authors: Wilson R F , Christensen B V , Olivari M T , Simon A , White C W , Laxson D D 
Published: June 2012

BACKGROUND
Cardiac transplantation (CT) causes total cardiac denervation.

METHODS AND RESULTS
To test directly for sympathetic reinnervation in humans, we measured the cardiac release of norepinephrine (NE) in response to tyramine (an agent that causes NE release from intact sympathetic nerve terminals) and sustained handgrip exercise (a reflex sympathetic stimulus) in 12 patients less than 5 months after CT, in 50 patients 1 year or more after CT, and in eight patients without CT. Plasma [NE] was measured in the aorta [( NE]Ao) and coronary sinus [( NE]CS) at rest, after tyramine administration (55 micrograms/kg, i.v.), and during sustained handgrip exercise. Cardiac NE release was determined by subtracting [NE]Ao from [NE]CS [( NE]CS-Ao). NE release was defined as [NE]CS-Ao during the intervention-[NE]CS-Ao at rest (delta [NE]CS-Ao). In patients studied within 5 months of CT, no significant NE release occurred after tyramine administration (delta [NE]CS-Ao, 33 +/- 18 pg/ml; range, -98 to 117 pg/ml) or handgrip exercise (delta [NE]CS-Ao, -34 +/- 10 pg/ml; range, -46 to 8 pg/ml; n = 10). Conversely, in 39 of 50 patients studied 1 year or more after CT, tyramine administration caused a significant cardiac NE release (delta [NE]CS-Ao, 500 +/- 59 pg/ml; range, -11 to 1,918 pg/ml), and handgrip exercise caused a significant NE release in 17 of 41 patients (delta [NE]CS-Ao, 189 +/- 34 pg/ml; range, -211 to 949 pg/ml). In normally innervated patients, tyramine caused an even larger NE release (delta [NE]Ao-CS, 1,943 +/- 210 pg/ml; range, 1,152 to 2,977 pg/ml), and handgrip exercise caused a significant NE release in two of seven patients (delta [NE]CS-Ao, 143 +/- 51 pg/ml; range, -15 to 338 pg/ml).

CONCLUSIONS
Early after CT, neither tyramine nor handgrip exercise caused a significant cardiac release of NE, suggesting sympathetic denervation. Late after CT, most patients had a significant, but subnormal, NE release in response to pharmacological or reflex stimuli, suggesting that limited sympathetic reinnervation occurs in most patients after orthotopic CT.
Patients with two types of atrioventricular junctional (AV nodal) reentrant tachycardia. Evidence that a common pathway of nodal tissue is not present above the reentrant circuit.
Authors: McGuire M A , Lau K C , Johnson D C , Richards D A , Uther J B , Ross D L 
Published: June 2012

BACKGROUND
The site of the reentrant circuit in atrioventricular (AV) junctional reentrant tachycardia has not been defined; in particular, the existence of a common pathway of AV nodal tissue above the reentrant circuit is controversial.

METHODS AND RESULTS
Two types of AV junctional reentrant tachycardia were induced in each of three patients at electrophysiological study. In one type of tachycardia (anterior), the onset of atrial activity occurred from 0 to 12 msec before the onset of ventricular activation, and earliest atrial activity was recorded near the His bundle. In the second type of tachycardia (posterior), the ventriculoatrial intervals were longer (76-168 msec), and earliest atrial activity was recorded near the mouth of the coronary sinus. In individual patients, the two types of tachycardia had different cycle lengths. Posterior AV junctional reentrant tachycardia was not a fast-slow form of AV junctional reentry in at least two of the three patients. Surgical cure was attempted in two patients. In one patient, anterior AV junctional reentrant tachycardia was abolished by dissection of the anterior perinodal atrium, but posterior AV junctional reentrant tachycardia could still be induced. At reoperation 4 months later, dissection of the posterior perinodal atrium abolished posterior AV junctional reentrant tachycardia while preserving AV conduction.

CONCLUSION
Differences in ventriculoatrial intervals and cycle lengths and the results of selective surgery suggest that the two types of AV junctional reentrant tachycardia used different reentrant circuits. These observations imply that a common pathway of AV nodal tissue is not present above the reentrant circuit and suggest that perinodal atrium is part of these circuits.
Screening for total cholesterol. Do the National Cholesterol Education Program's recommendations detect individuals at high risk of coronary heart disease?
Authors: Bush T L , Riedel D 
Published: June 2012

BACKGROUND
The National Cholesterol Education Program (NCEP) has provided guidelines for identification of persons at high risk of coronary heart disease (CHD) because of lipid abnormalities. These recommendations are based on total cholesterol as the initial screening tool and have become the stimulus for clinic- and community-based screening programs nationwide. However, the use of the guidelines may be problematic because individuals may have total cholesterol levels in the desirable range but low density lipoprotein (LDL) or high density lipoprotein (HDL) levels considered at high risk. This study evaluates the ability of the NCEP screening recommendations to identify correctly persons at high risk of CHD because of lipid abnormalities.

METHODS AND RESULTS
Using the NCEP guidelines, we simulated a population-based screening program with data from visits 1 and 2 of the Lipid Research Clinics Program Prevalence Study. Individuals were considered to be at high risk of CHD if they had LDL levels greater than 160 mg/dl or HDL levels less than 35 mg/dl. Following the NCEP process, 21% of those with high LDL concentrations and 66% of those with low HDL concentrations would not be routinely referred for immediate treatment. Overall, 41% of those at high risk of CHD would not be promptly evaluated. The sensitivity of the guidelines for promptly identifying individuals with lipoprotein abnormalities is 59%.

CONCLUSIONS
This relatively low sensitivity of total cholesterol as a screening tool should be the impetus for rethinking the screening guidelines. Specifically, the cost-benefit ratio of routine screening for lipoproteins, particularly HDL cholesterol, needs to be carefully considered.
Oral administration of DuP 753, a specific angiotensin II receptor antagonist, to normal male volunteers. Inhibition of pressor response to exogenous angiotensin I and II.
Authors: Christen Y , Waeber B , Nussberger J , Porchet M , Borland R M , Lee R J , Maggon K , Shum L , Timmermans P B , Brunner H R 
Published: June 2012

BACKGROUND
The purpose of the present study was to assess the inhibitory effect of DuP 753, an orally active angiotensin II receptor antagonist, on the pressor action of exogenous angiotensin I and II in healthy male volunteers.

METHODS AND RESULTS
In the first study (single-dose study), eight volunteers were included in a 2-day protocol repeated four times at 1-week intervals. In each phase, a different dose of drug (2.5, 5, 10, 20, or 40 mg) or placebo was given. The peak systolic blood pressure response to a test-dose of angiotensin I was determined serially before and after oral administration of DuP 753 by continuously monitoring finger blood pressure using a photoplethysmographic method. DuP 753 reduced the systolic blood pressure response to angiotensin I in a dose-dependent fashion. Three, 6, and 13 hours after the 40-mg dose, blood pressure response decreased to 31 +/- 5%, 37 +/- 6%, and 45 +/- 3% of the control values (mean +/- SEM, n = 7), respectively. In the second study, 29 volunteers were treated for 8 days with either a placebo or DuP 753 (5, 10, 20, or 40 mg p.o. q.d.) and challenged on the first, fourth, and eighth days with bolus injections of angiotensin II. Again, the inhibitory effect on the systolic blood pressure response to angiotensin II was clearly dose dependent. Six hours after 40 mg DuP 753, the systolic blood pressure response to the test-dose of angiotensin II was reduced to 37 +/- 7%, 40 +/- 4%, and 38 +/- 6% of baseline values (mean +/- SEM, n = 6) on days 1, 4, and 8, respectively. With this latter dose, there was still a blocking effect detectable 24 hours after the drug. Similar to angiotensin converting enzyme and renin inhibitors, DuP 753 induced a dose-dependent increase in plasma renin that was more pronounced on the eighth than on the first day of drug administration. In these normal volunteers, no consistent clinically significant side effects were observed. There was no evidence for an agonist effect.

CONCLUSIONS
DuP 753 appears to be a well-tolerated, orally active, potent, and long-lasting antagonist of angiotensin II in men.