bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic dissection of puberty in mice
Authors: Kumar Devesh , Boehm Ulrich 
Published: August 2013

New Findings
What is the topic of this review? How is the timely reactivation of gonadotrophin‐releasing hormone neurons at puberty regulated?
What advances does it highlight? Conditional ablation of the oestrogen receptor α gene in kisspeptin neurons results in a dramatic advancement of the onset of puberty in female mice, but subsequent pubertal maturation is arrested in these animals, as they fail to acquire normal ovulatory cyclicity. In contrast, the onset of puberty in female mice was unaffected by kisspeptin neuron ablation. Furthermore, the animals attained regular ovulatory cyclicity and were fertile. Consistent with this, female mice lacking neurons that express the kisspeptin receptor GPR54 were also fertile, suggesting female reproductive maturation in the absence of kisspeptin/GPR54 signalling.
Determining the neural mechanisms controlling gonadotrophin‐releasing hormone (GnRH) release is of pivotal importance in understanding central control of reproductive physiology in vertebrates. Targeted genetic manipulation of kisspeptin and GPR54 neurons has provided new insights into the mechanisms modulating GnRH release and thereby regulating hypothalamic–pituitary–gonadal axis activity during reproductive maturation. While conditional ablation of the oestrogen receptor α gene in kisspeptin neurons results in a dramatic advancement of the onset of puberty in female mice, subsequent pubertal maturation is arrested in these animals, as they fail to acquire normal ovulatory cyclicity. These data suggest that two oestrogen receptor α‐dependent mechanisms, one a ‘brake’ and the other an ‘accelerator’, are sequentially operated in kisspeptin neurons during pubertal development of female mice to gate and then to activate GnRH release. In a different experimental approach, we removed entire kisspeptin neurons from the mouse brain and thus from the neural circuits controlling reproduction. Surprisingly, the onset of puberty in females was unaffected by kisspeptin neuron ablation. Furthermore, the animals attained regular ovulatory cyclicity and were fertile. Consistent with this, female mice lacking neurons that express the kisspeptin receptor GPR54 were also fertile, suggesting female reproductive maturation in the absence of kisspeptin/GPR54 signalling. However, acute kisspeptin neuron ablation in adult mice inhibited fertility, indicating that there is developmental compensation for the loss of kisspeptin neurons during reproductive neural circuit formation. Finally, we showed that kisspeptin neurons become an indispensable part of reproductive neural circuitry in the mouse brain before postnatal day 20.
Physiology of invertebrate oxytocin and vasopressin neuropeptides
Authors: Gruber Christian W. 
Published: August 2013

New findings
What is the topic of this review?This article describes the discovery and function of invertebrate oxytocin and vasopressin neuropeptides.
What advances does it highlight?The novel discovery of oxytocin‐like peptides in arthropods is described. An up‐to date overview is gven of the functional role (physiology and behaviour) of oxytocin and vasopressin signalling. The application of natural peptides for drug development is discussed.
Neuropeptides and regulatory peptide hormones control many developmental, physiological and behavioural processes in animals, including humans. The nonapeptides oxytocin and arginine vasopressin are produced and released by the pituitary gland and have actions on many organs and tissues. Receptive cells possess particular receptors to which the peptides bind as ligands, leading to activation of G‐protein‐coupled receptors, hence cellular responses. In humans and other mammalian species, oxytocin and vasopressin mediate a range of peripheral and central physiological functions that are important for osmoregulation, reproduction, complex social behaviours, memory and learning. The origin of the oxytocin/vasopressin signalling system is thought to date back more than 600 million years. All vertebrate oxytocin‐ and vasopressin‐like peptides have presumably evolved from the ancestral nonapeptide vasotocin by gene duplication and today are present in vertebrates, including mammals, birds, reptiles, amphibians and fish. Oxytocin‐ and vasopressin‐like peptides have been identified in several invertebrate species, including molluscs, annelids, nematodes and arthropods. Members of this peptide family share high sequence similarity, and it is possible that they are functionally related across the entire animal kingdom. However, it is evident that not all animals express oxytocin/vasopressin neuropeptides and that there is little information available about the biology and physiology of this signalling system of invertebrates and, in particular, of insects, which represent more than half of all known living organisms. This report describes the discovery of novel oxytocin‐ and vasopressin‐like peptides in arthropods and summarizes the status quo of the functional relevance of this neuropeptide signalling system in invertebrates, which will have beneficial implications for the design of selective and potent ligands to human oxytocin and vasopressin receptors.
The neural regulation of the kidney in hypertension and renal failure
Authors: Johns Edward J. 
Published: August 2013

New Findings
What is the topic of this review?
Reports that bilateral renal denervation in resistant hypertensive patients results in a long‐lasting reduction in blood pressure raise the question of the underlying mechanisms involved and how they may be deranged in pathophysiological states of hypertension and renal failure.
What advances does it highlight?
The renal sensory afferent nerves and efferent sympathetic nerves work together to exert an important control over extracellular fluid volume, hence the level at which blood pressure is set. This article emphasizes that both the afferent and the efferent renal innervation may contribute to the neural dysregulation of the kidney that occurs in chronic renal disease and resistant hypertension.
Autonomic control is central to cardiovascular homeostasis, and this is exerted not only at the level of the heart and blood vessels but also at the kidney. At the kidney, the sympathetic neural regulation of renin release and fluid reabsorption may influence fluid balance and, in the longer term, the level at which blood pressure is set. The role of the renal innervation in the regulation of blood pressure has received renewed attention over the past few years, following the reports that bilateral renal denervation of resistant hypertensive patients resulted in a marked reduction in blood pressure, which has been maintained for several years. Such has been the interest that this approach of renal denervation is being applied in other patient groups with diabetes, obesity and renal failure, with the hope that there may be a sustained reduction in blood pressure as well as the amelioration of some aspects of the metabolic syndrome. However, the factors that come into play to cause the rise in blood pressure in these patient groups, particularly the resistant hypertensive patients, are far from clear. Moreover, the mechanisms leading to the fall in blood pressure following renal denervation of resistant hypertensive patients currently elude our understanding and is therefore an area that requires much more investigation to enhance our insight.
Effect of vasopressin on the expression of genes for key enzymes of hyaluronan turnover in Wistar Albino Glaxo and Brattleboro rat kidneys
Authors: Ivanova Lyudmila N. , Babina Alina V. , Baturina Galina S. , Katkova Lyubov E. 
Published: August 2013

New findings
What is the central question of this study?The interstitium of the renal inner medulla contains abundant linear negatively charged glycosaminoglycan hyaluronan (HA), which affects the water flow depending on their polymeric state. It remains an open question whether HA is involved in the long‐term effect of vasopressin on water reabsorption via the regulation of the expression of genes for key enzymes of HA turnover.
What is the main finding and its importance?Using real‐time RT‐PCR, we show that in rats vasopressin inhibits the synthesis of HA and concomitantly promotes its degradation in the renal interstitium through its effect on genes for key enzymes of HA turnover (hyaluronan synthase‐2 and hyaluronidase‐2). Analysis of the long‐term effect of vasopressin on the transcription of these genes demonstrated a new mechanism in hormonal regulation of the renal concentrating function.
Hyaluronan (HA), the major glycosaminoglycan of the interstitial matrix, is heterogeneously distributed within the kidney. Using real‐time RT‐PCR, we tested the assumption that renal HA may be involved in the long‐term effect of vasopressin on water reabsorption. The expression of the genes encoding hyaluronan synthase‐2 (Has2), hyaluronidase‐1 and hyaluronidase‐2 (Hyal1 and Hyal2) was studied in the kidneys of Wistar Albino Glaxo (WAG) and homozygous vasopressin‐deficient Brattleboro rats treated with the V2 receptor‐selective vasopressin analogue dDAVP (100 μg (kg body wt)−1, i.p., twice a day for 2 days). The Has2 mRNA content was the highest in the kidney papilla of the hydrated WAG and control Brattleboro rats, devoid of vasopressin. In WAG rats, dDAVP induced a considerable decrease in Has2 mRNA content in the papilla, with less pronounced changes in the cortex. The changes elicited by dDAVP in Brattleboro rats tended to be the same as in WAG rats, but weaker. In contrast to Has2, dDAVP treatment caused a significant increase in the Hyal1 and Hyal2 mRNA content in the renal papilla of WAG and Brattleboro rats. In rats of both strains, there was a good fit between Hyal1 and Hyal2 transcriptional levels and changes in hyaluronidase activity in the renal tissue. It is suggested that vasopressin is able to inhibit the synthesis of HA and concomitantly promote its degradation in the interstitium of the renal papilla, thereby facilitating water flow between elements of the renal countercurrent system. The implications for this effect are discussed in the context of the data in the literature.
Admittance‐based pressure–volume loop measurements in a porcine model of chronic myocardial infarction
Authors: van Hout G. P. J. , de Jong R. , Vrijenhoek J. E. P. , Timmers L. , Duckers H. J. , Hoefer I. E. 
Published: August 2013

New Findings
What is the central question of this study?Are admittance‐based pressure–volume measurements useful for the assessment of cardiac function in a chronic myocardial infarction model compared with three‐dimensional echocardiography and with classical conductance measurements?
What is the main finding and its importance?Baseline admittance‐based measurements show good agreement with echocardiography and classical conductance in human‐sized porcine hearts. Myocardial infarction significantly alters ventricular dimensions and pressure–volume loop measurements compared with three‐dimensional echocardiography. The novel admittance system reliably monitors changes in cardiac function after myocardial infarction.
The aim of this study was to validate admittance‐based pressure–volume (PV) loop measurements for the assessment of cardiac function in a porcine model of chronic myocardial infarction. The traditional PV loop measurement technique requires hypertonic saline injections for parallel conductance correction prior to signal conversion into volume. Furthermore, it assumes a linear relationship between conductance and volume. More recently, an admittance‐based technique has been developed, which continuously measures parallel conductance and uses a non‐linear equation for volume calculation. This technique has not yet been evaluated in a large‐animal model of myocardial ischaemia. Eleven pigs underwent invasive PV measurements with the admittance system (AS) and the traditional conductance system followed by three‐dimensional echocardiography (3DE). After baseline measurements, pigs were subjected to 90 min left anterior descending coronary artery occlusion, followed by the same measurements at 8 weeks follow‐up. In the healthy heart, the AS showed good agreement with 3DE for left ventricular volumes and a reasonable correlation for ejection fraction (r= 0.756, P= 0.007). At follow‐up, an increase in end‐systolic volume was observed with 3DE (+15.4 ± 14.4 ml, P= 0.005) and the AS (+34.6 ± 36.1 ml, P= 0.010). The ejection fraction measured with 3DE (−13.2 ± 5.2%, P < 0.001) and the AS (−20.3 ± 11.2%, P < 0.001) significantly decreased. We conclude that the AS can be used for quantitative monitoring of changes in cardiac function induced by myocardial infarction and provides comparable results to 3DE, rendering it a useful tool for functional testing in large‐animal cardiac models.
Modulation of food intake by mTOR signalling in the dorsal motor nucleus of the vagus in male rats: focus on ghrelin and nesfatin‐1
Authors: Zhang Weizhen , Zhang Chao , Fritze Danielle , Chai Biaoxin , Li Jiyao , Mulholland Michael W. 
Published: August 2013

New findings
What is the central question of this study?Does mammalian target of rapamycin (mTOR) signalling in the dorsal vagal complex contribute to the modulation of energy homeostasis?
What is the main finding and its importance?Our study shows, for the first time, that mTOR signalling in neurons of the dorsal motor nucleus of the vagus regulates both the nutrient and the hormonal signals for the modulation of food intake. These results imply that mTOR signalling in the hindbrain may serve as a potential target for treatment of obesity and appetite‐related disorders.
Previous studies have demonstrated that mammalian target of rapamycin (mTOR) signalling in the hypothalamus is involved in the control of energy homeostasis. The aim of this study was to characterize the effect of mTOR signalling in the dorsal motor nucleus of the vagus (DMNV) on energy intake. Phospho‐mTOR was detected in the DMNV neurons, and its levels were increased by energy deprivation. Rapamycin significantly inhibited mTOR activity and reduced food intake when administrated into the fourth ventricle. Exposure of DMNV neurons to ghrelin increased the phosphorylation of mTOR. Injection of ghrelin into the fourth ventricle significantly increased food intake relative to the control vehicle. Pretreatment with rapamycin for 15 min attenuated the orexigenic effect of ghrelin. A reduction in the phosphorylation of mTOR was observed following injection of nesfatin‐1 into the fourth ventricle. When administrated by injection into the fourth ventricle, nesfatin‐1 suppressed food intake in comparison with the control vehicle. The anorexigenic effect of nesfatin‐1 was significantly attenuated by pretreatment with leucine for 15 min. All these findings suggest that mTOR signalling in the DMNV neurons regulates both the nutrient and the hormonal signals for the modulation of food intake.
Phosphatidylethanolamine binding protein 1 in vacular endothelial cell autophagy and atherosclerosis
Authors: Wang Li , Li HaiYing , Zhang JinFeng , Lu Wei , Zhao Jing , Su Le , Zhao BaoXiang , Zhang Yun , Zhang ShangLi , Miao JunYing 
Published: August 2013

Key points
The enzyme phosphatidylcholine‐specific phospholipase C (PC‐PLC) participates in atherosclerosis development and may negatively regulate autophagy.
Phosphatidylethanolamine binding protein 1 (PEBP1) represents a novel effector of signal transduction pathways that control cellular growth, motility, apoptosis, genomic integrity, and therapeutic resistance.
The disruption of PEBP1 was reported to associate with a wide range of diseases, such as cancer, pancreatitis, and Alzheimer's disease, making it a potential target for disease therapy. However, the roles of PEBP1 in vascular endothelial cell (VEC) autophagy and arteriosclerosis are not clear.
Here we report that PEBP1 interacts with PC‐PLC and positively regulates PC‐PLC activity, while both PEBP1 and PC‐PLC negatively regulate VEC autophagy.
The PEBP1 level is elevated during the development of atherosclerosis, and the PC‐PLC inhibitor D609 significantly decreases the upregulated PEBP1 level in apolipoprotein E−/− mice, suggesting that PEBP1 may be a potential diagnostic indicator for atherosclerosis.
Abstract  We previously found that phosphatidylcholine‐specific phospholipase C (PC‐PLC) was a key inducing element of atherosclerosis, and might negatively regulate human umbilical vein endothelial cell (HUVEC) autophagy. To further investigate the mechanism of PC‐PLC action, we initially identified phosphatidylethanolamine binding protein 1 (PEBP1) as a binding partner of PC‐PLC by using mass spectrometry (MS, MALDI‐TOF/TOF). We found that PEBP1 positively regulated PC‐PLC activity in HUVECs, and inhibition of PC‐PLC by its inhibitor D609 suppressed PEBP1 expression dramatically. Moreover, both PC‐PLC and PEBP1 negatively regulated HUVEC autophagy independently of mammalian target of rapamycin (mTOR). Furthermore, the PEBP1 level was elevated during the development of atherosclerosis, while D609 significantly decreased the upregulated PEBP1 level in apoE−/− mice.
Whole-Genome Sequencing of Gentamicin-Resistant Campylobacter coli Isolated from U.S. Retail Meats Reveals Novel Plasmid-Mediated Aminoglycoside Resistance Genes
Authors: Chen Yuansha , Mukherjee Sampa , Hoffmann Maria , Kotewicz Michael L , Young Shenia , Abbott Jason , Luo Yan , Davidson Maureen K. , Allard Marc , McDermott Patrick , Zhao Shaohua 
Published: August 2013

ABSTRACT

Aminoglycoside resistance in
Campylobacter
has been routinely monitored in the United States in clinical isolates since 1996 and in retail meats since 2002. Gentamicin resistance first appeared in a single human isolate of
Campylobacter coli
in 2000 and in a single chicken meat isolate in 2007, after which it increased rapidly to account for 11.3% of human isolates and 12.5% of retail isolates in 2010. Pulsed-field gel electrophoresis analysis indicated that gentamicin-resistant
C. coli
isolates from retail meat were clonal. We sequenced the genomes of two strains of this clone using a next-generation sequencing technique in order to investigate the genetic basis for the resistance. The gaps of one strain were closed using optical mapping and Sanger sequencing, and this is the first completed genome of
C. coli
. The two genomes are highly similar to each other. A self-transmissible plasmid carrying multiple antibiotic resistance genes was revealed within both genomes, carrying genes encoding resistance to gentamicin, kanamycin, streptomycin, streptothricin, and tetracycline. Bioinformatics analysis and experimental results showed that gentamicin resistance was due to a phosphotransferase gene,
aph(2″)-Ig
, not described previously. The phylogenetic relationship of this newly emerged clone to other
Campylobacter
spp. was determined by whole-genome single nucleotide polymorphisms (SNPs), which showed that it clustered with the other poultry isolates and was separated from isolates from livestock.
The Mevalonate Auxotrophic Mutant of Staphylococcus aureus Can Adapt to Mevalonate Depletion
Authors: Yu Wenqi , Leibig Martina , Schäfer Tina , Bertram Ralph , Ohlsen Knut , Götz Friedrich 
Published: August 2013

ABSTRACT

In this study, we attempted to adopt the auxotrophic mevalonate synthase mutant (Δ
mvaS
mutant) of
Staphylococcus aureus
to study whether a nongrowing but viable cell population is tolerant to bactericidal antibiotics. The mevalonate-depleted nongrowing Δ
mvaS
mutant was found tolerant to antibiotics. Surprisingly, after prolonged cultivation, we obtained stable Δ
mvaS
variants that were able to grow without mevalonate, which suggested unknown mechanisms for compensating undecaprenyl pyrophosphate production without mevalonate in
S. aureus
.
Regional Resistance Surveillance Program Results for 12 Asia-Pacific Nations (2011)
Authors: Mendes Rodrigo E. , Mendoza Myrna , Banga Singh Kirnpal K. , Castanheira Mariana , Bell Jan M. , Turnidge John D. , Lin Stephen S. F. , Jones Ronald N. 
Published: August 2013

ABSTRACT

The Regional Resistance Surveillance program monitored susceptibility rates and developing resistance by geographic region, including 12 Asia-Pacific (APAC) countries. Reference broth microdilution methods for susceptibility/interpretations were applied, processing 5,053 strains. Among
Staphylococcus aureus
isolates (37% methicillin-resistant
S. aureus
[MRSA], highest in South Korea [73%]), linezolid (LZD), tigecycline (TIG), and vancomycin were 100% active, but 33 and 34% of strains were levofloxacin (LEV) or macrolide resistant, respectively.
Streptococcus pneumoniae
was most resistant to β-lactams and macrolides (45%) but was LZD, LEV, and TIG susceptible (>98%). Extended-spectrum β-lactamase (ESBL) phenotype rates in
Escherichia coli
and
Klebsiella
spp. were 48 and 47%, respectively, and were highest in Taiwan, at 75 to 91%. The best anti-ESBL-phenotype agents were amikacin (81 to 96% susceptible), colistin (COL; >98%), TIG (>98%), and carbapenems (81 to 97%).
Pseudomonas aeruginosa
showed ≥20% resistance to all drugs except COL (99% susceptible). In conclusion, endemic evolving antimicrobial resistances in APAC nations show compromised roles for many commonly used antimicrobials.
Subtyping of a Large Collection of Historical Listeria monocytogenes Strains from Ontario, Canada, by an Improved Multilocus Variable-Number Tandem-Repeat Analysis (MLVA)
Authors: Saleh-Lakha S. , Allen V. G. , Li J. , Pagotto F. , Odumeru J. , Taboada E. , Lombos M. , Tabing K. C. , Blais B. , Ogunremi D. , Downing G. , Lee S. , Gao A. , Nadon C. , Chen S. 
Published: August 2013

ABSTRACT

Listeria monocytogenes
is responsible for severe and often fatal food-borne infections in humans. A collection of 2,421
L. monocytogenes
isolates originating from Ontario's food chain between 1993 and 2010, along with Ontario clinical isolates collected from 2004 to 2010, was characterized using an improved multilocus variable-number tandem-repeat analysis (MLVA). The MLVA method was established based on eight primer pairs targeting seven variable-number tandem-repeat (VNTR) loci in two 4-plex fluorescent PCRs. Diversity indices and amplification rates of the individual VNTR loci ranged from 0.38 to 0.92 and from 0.64 to 0.99, respectively. MLVA types and pulsed-field gel electrophoresis (PFGE) patterns were compared using Comparative Partitions analysis involving 336 clinical and 99 food and environmental isolates. The analysis yielded Simpson's diversity index values of 0.998 and 0.992 for MLVA and PFGE, respectively, and adjusted Wallace coefficients of 0.318 when MLVA was used as a primary subtyping method and 0.088 when PFGE was a primary typing method. Statistical data analysis using BioNumerics allowed for identification of at least 8 predominant and persistent
L. monocytogenes
MLVA types in Ontario's food chain. The MLVA method correctly clustered epidemiologically related outbreak strains and separated unrelated strains in a subset analysis. An MLVA database was established for the 2,421
L. monocytogenes
isolates, which allows for comparison of data among historical and new isolates of different sources. The subtyping method coupled with the MLVA database will help in effective monitoring/prevention approaches to identify environmental contamination by pathogenic strains of
L. monocytogenes
and investigation of outbreaks.