bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constructing abelian surfaces for cryptography via Rosenhain invariants
Authors: Costello Craig , Deines-Schartz Alyson , Lauter Kristin , Yang Tonghai 
Published: August 2014

AbstractThis paper presents an algorithm to construct cryptographically strong genus $\def \xmlpi #1{}\def \mathsfbi #1{\boldsymbol {\mathsf {#1}}}\let \le =\leqslant \let \leq =\leqslant \let \ge =\geqslant \let \geq =\geqslant \def \Pr {\mathit {Pr}}\def \Fr {\mathit {Fr}}\def \Rey {\mathit {Re}}2$ curves and their Kummer surfaces via Rosenhain invariants and related Kummer parameters. The most common version of the complex multiplication (CM) algorithm for constructing cryptographic curves in genus 2 relies on the well-studied Igusa invariants and Mestre’s algorithm for reconstructing the curve. On the other hand, the Rosenhain invariants typically have much smaller height, so computing them requires less precision, and in addition, the Rosenhain model for the curve can be written down directly given the Rosenhain invariants. Similarly, the parameters for a Kummer surface can be expressed directly in terms of rational functions of theta constants. CM-values of these functions are algebraic numbers, and when computed to high enough precision, LLL can recognize their minimal polynomials. Motivated by fast cryptography on Kummer surfaces, we investigate a variant of the CM method for computing cryptographically strong Rosenhain models of curves (as well as their associated Kummer surfaces) and use it to generate several example curves at different security levels that are suitable for use in cryptography.
Intestinal regulation of urinary sodium excretion and the pathophysiology of diabetic kidney disease: a focus on glucagon‐like peptide 1 and dipeptidyl peptidase 4
Authors: Vallon Volker , Docherty Neil G. 
Published: August 2014

New Findings
What is the topic of this review?
This review describes how hyperglycaemia and attendant increases in proximal tubular growth and sodium reclamation form the mechanistic basis for the tubular hypothesis of hyperfiltration and nephropathy in the kidneys of patients with diabetes. The review highlights how signals arising from the gastrointestinal tract may be capable of modulating this response and how pharmacological enhancement of these signals may ameliorate the progression of diabetic kidney disease.
What advances does it highlight?
The review highlights the potential of glucagon‐like peptide 1 analogues, glucagon‐like peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors to exercise renoprotective effects in diabetes independent of their classical effects on endocrine pancreas.
The tubular hypothesis of glomerular filtration and nephropathy in diabetes is a pathophysiological concept that assigns a critical role to the tubular system, including proximal tubular hyper‐reabsorption and growth, which is relevant for early glomerular hyperfiltration and later chronic kidney disease. Here we focus on how harnessing the bioactivity of hormones released from the gut may ameliorate the early effects of diabetes on the kidney in part by attenuating proximal tubular hyper‐reabsorption and growth. The endogenous tone of the glucagon‐like peptide 1 (GLP‐1)/GLP‐1 receptor (GLP‐1R) system and its pharmacological activation are nephroprotective in diabetes independent of changes in blood glucose. This is associated with suppression of increases in kidney weight and glomerular hyperfiltration, which may reflect, at least in part, its inhibitory effects on tubular hyper‐reabsorption and growth. Inhibition of dipeptidyl peptidase 4 (DPP‐4) is also nephroprotective independent of changes in blood glucose and involves GLP‐1/GLP‐1R‐dependent and ‐independent mechanisms. The GLP‐1R agonist exendin‐4 induces natriuresis via activation of the GLP‐1R. In contrast, DPP4 inhibition increases circulating GLP‐1, but drives a GLP‐1R‐independent natriuretic response, implying a role for other DPP‐4 substrates. The extent to which the intrarenal DPP‐4/GLP‐1 receptor system contributes to all these changes remains to be established, as does the direct impact of the system on renal inflammation.
Targeting cellular drivers and counter‐regulators of hyperglycaemia‐ and transforming growth factor‐β1‐associated profibrotic responses in diabetic kidney disease
Authors: Docherty Neil G. , Murphy Madeline , Martin Finian , Brennan Eoin P. , Godson Catherine 
Published: August 2014

New Findings
What is the topic of this review?
Through reference to specific lines of investigation, this review sets out the case for how understanding the drivers and endogenous counter‐regulators of inflammatory and fibrotic responses can identify novel targets for inhibition or mimicry in diabetic kidney disease.
What advances does it highlight?
The review highlights the potential of induced in high glucose‐1 (IHG‐1) and induced in high glucose‐2 (IHG‐2/Grem1) to act as drugable targets in transforming growth factor‐β superfamily signalling in diabetic kidney disease. It also describes the preclinical evidence base for the fibrosupressant effects of the resolvent lipoxin series of eicosanoids in diabetic kidney disease, highlighting the role of a novel and specific microRNA‐based effect on transforming growth factor‐β1 signalling.
Diabetic kidney disease occurs in >30% of patients with type 2 diabetes mellitus and is characterized at source by a maladaptive response in the renal parenchyma to exposure to a glucotoxic–lipotoxic diabetic milieu that courses coincident with hypertension. The consequence of these maladaptive responses is progressive renal injury, which is exacerbated by the development of a chronic inflammatory infiltrate associated with the development of tubulointerstitial fibrosis. The evolution of tubulointerstitial fibrosis is correlated with the loss of functional renal mass and descent towards renal failure. Transforming growth factor‐β1 (TGF‐β1) is a recognized mediator of the profibrotic response of mesangial cells and renal tubular epithelial cells to hyperglycaemia. While euglycaemia remains the goal in the treatment of type 2 diabetes mellitus, the prevention, arrest and reversal of microvascular complications, such as diabetic kidney disease, may be assisted by pharmacological modulation of the effectors of glucotoxicity, such as TGF‐β1. This review focuses on describing how, through reductionist in vitro experimentation focusing on TGF‐β1‐related responses to hyperglycaemia, we have identified induced in high glucose‐1 (IHG‐1), induced in high glucose‐2 (IHG‐2/Grem1) and the lipoxin‐inducible microRNA let‐7c as potential targets for harnessing new therapeutic approaches to limit the bioactivity of TGF‐β1 in diabetic kidney disease.
Improvements in the metabolic milieu following Roux‐en‐Y gastric bypass and the arrest of diabetic kidney disease
Authors: Docherty Neil G. , le Roux Carel W. 
Published: August 2014

New Findings
What is the topic of this review?
This review outlines the indications for use of Roux‐en‐Y gastric bypass as a bariatric and metabolic procedure, addressing the evidence and proposed mechanisms for improvements in the metabolic milieu and blood pressure control. Evidence to date supportive of a role for Roux‐en‐Y gastric bypass in the arrest of diabetic kidney disease follows with a perspective on mechanisms involved and their potential to be replicated in the non‐surgical setting.
What advances does it highlight?
The review highlights evidence supportive of the potential efficacy of Roux‐en‐Y gastric bypass in preventing progression of early diabetic kidney disease in patients with obesity and type 2 diabetes.
Roux‐en‐Y gastric bypass (RYGB) is an efficacious intervention for morbid obesity and has a diabetes‐remitting effect in patients with obesity and type 2 diabetes mellitus, which occurs prior to significant weight loss. Roux‐en‐Y gastric bypass is also associated with early and sustained reductions in the risk factor profile for the progression of diabetic complications. Attention is therefore now being placed on RYGB as a metabolic intervention with the capacity to yield therapeutic benefit in relation to the progression of diabetic complications, such as diabetic kidney disease. As alterations in gut anatomy following RYGB coincide with attendant shifts in downstream enteroendocrine signals with direct and indirect resolutionary effects on the kidney, the concept of an endocrine gut–kidney axis post‐RYGB is growing. With the model of a gut–kidney axis in mind, this article summarizes emerging data on the effects of RYGB on risk factors for diabetic kidney disease (hyperglycaemia, dyslipidaemia and hypertension), highlighting a potential role for glucagon‐like peptide 1 in risk factor reduction.
Advanced onset of puberty after metformin therapy in swine with thrifty genotype
Authors: Astiz S. , Gonzalez‐Bulnes A. , Astiz I. , Barbero A. , Perez‐Solana M.L. , Garcia‐Real I. 
Published: August 2014

New Findings
What is the central question of this study?
What is the effect of prepuberal metformin therapy and lifestyle in an obese swine model (Iberian gilts) with thrifty genotype on patterns of growth, fattening, metabolic status and attainment of puberty?
What is the main finding and its importance?
An obesogenic diet had deleterious effects on corpulence, adiposity and metabolic parameters. These features were favourably modulated by adequate lifestyle and metformin treatment, which favoured muscle deposition. However, metformin advanced the onset of puberty, which would be a negative effect. This provides a warning about the use of metformin, without further studies, in girls from ethnicities with thrifty genotype.
The prevention and treatment of obesity in children is based on adequate nutrition and exercise plus antihyperglycaemic drugs. Currently, the incidence of childhood obesity is aggravated in ethnicities with thrifty genotype, but there is no available information on the effects of metformin therapy. The relative effects of lifestyle and metformin on patterns of growth, fattening, metabolic status and attainment of puberty were assessed in females of an obese swine model (Iberian gilts), allocated to three experimental groups (group A, obesogenic diet and scarce exercise; group DE, adequate diet and opportunity for exercise; and group DEM, adequate diet and opportunity for exercise plus metformin). Group A evidenced high weight, corpulence and adiposity, high plasma triglycerides and impairments of glucose regulation predisposing to insulin resistance. These features were favourably modulated by adequate lifestyle (group DE), and these effects were strengthened by metformin treatment (group DEM), which induced an improvement in body development by favouring muscle deposition. However, contrary to expectations, metformin advanced the onset of puberty. Metformin treatments would have positive effects on growth patterns, adiposity and metabolic features of young females from ethnicities with thrifty genotype or developing leptin resistance, but a negative effect by advancing the attainment of puberty. This study provides a warning regarding the use of metformin, without further studies, in girls from these ethnicities.
ON‐pathway‐dominant glycinergic regulation of cholinergic amacrine cells in the mouse retina
Authors: Ishii Toshiyuki , Kaneda Makoto 
Published: August 2014

Key points
Starburst amacrine cells (SACs) in the retina play a key role for the formation of direction selectivity and considered a good model of neural computation.
Although SACs distribute in both ON‐ and OFF‐pathway, only the physiological properties of SACs in ON‐pathway have been well characterized.
As the physiological properties of SACs in the OFF‐pathway were not well known, in this study, we directly compared the inputs of SACs in ON‐ and OFF‐pathways.
Here we report a novel finding that glycinergic inputs onto SACs were ON‐pathway dominant, while glutamatergic inputs were equivalent between ON‐ and OFF‐pathway.
Our results suggest that fully defining the physiological properties of SACs in both ON‐ and OFF‐pathway will be critical to understanding and modelling direction selectivity in the retina.
AbstractDirection selectivity in the retina has been studied as a model of dendritic computation of neural circuits. Starburst amacrine cells (SACs) have been examined as a model system of dendritic computation as they play a pivotal role in the formation of direction selectivity. Because the difference of anatomical location inside the retina made ON‐SACs an easier target to record, the biophysical properties of ON‐SACs have been used to predict those of OFF‐SACs. In this study, we systematically compared the responses of ON‐ and OFF‐SACs to the two principal neurotransmitters, glycine and glutamate. We found that responses to glycine were significantly larger in ON‐SACs than in OFF‐SACs. In contrast, ON‐ and OFF‐SACs responded similarly to glutamate. The amplitude of glycine responses in ON‐SACs increased after eye opening and the largest amplitude was observed at postnatal day 28. On the other hand, no increase in the amplitude of glycine responses in OFF‐SACs was observed until postnatal day 28. Glycine‐evoked currents were inhibited by the application of strychnine. Glutamate‐evoked currents were mimicked by the application of AMPA or kainite, and responses to N‐methyl‐d‐aspartate were observed in the absence of Mg2+ block. Glutamate‐evoked currents produced an increase in the frequency of GABAergic inhibitory postsynaptic currents. Our results suggest that signal processing in ON‐SACs cannot be directly used to understand the properties of OFF‐SACs. Therefore fully defining the physiological properties of OFF‐SACs will be critical to understanding and modelling direction selectivity in the retina.
Increased cardiac output, not pulmonary artery systolic pressure, increases intrapulmonary shunt in healthy humans breathing room air and 40% O2
Authors: Elliott Jonathan E. , Duke Joseph W. , Hawn Jerold A. , Halliwill John R. , Lovering Andrew T. 
Published: August 2014

Key points
The contribution of blood flow through intrapulmonary arteriovenous anastomoses (IPAVAs) to pulmonary gas exchange efficiency remains unknown and controversial.
Intravenous infusion of adrenaline (epinephrine) increases blood flow through IPAVAs detected by the transpulmonary passage of saline contrast and breathing 40% O2 minimizes potential contributions from ventilation‐to‐perfusion inequality and diffusion limitation.
Pulmonary gas exchange efficiency was impaired to the same degree, and the transpulmonary passage of saline contrast was not different, in humans at rest during the intravenous infusion of adrenaline before and after atropine when breathing room air and 40% O2.
Cardiac output increased to the same degree during intravenous infusion of adrenaline before and after atropine, but pulmonary artery systolic pressure only increased significantly before atropine.
These data demonstrate that blood flow through IPAVAs contributes to pulmonary gas exchange efficiency and that blood flow through IPAVAs is predominantly mediated by increases in cardiac output rather than increases in pulmonary artery systolic pressure.
AbstractBlood flow through intrapulmonary arteriovenous anastomoses (IPAVAs) has been demonstrated to increase in healthy humans during a variety of conditions; however, whether or not this blood flow represents a source of venous admixture (/) that impairs pulmonary gas exchange efficiency (i.e. increases the alveolar‐to‐arterial difference (A–aDO2)) remains controversial and unknown. We hypothesized that blood flow through IPAVAs does provide a source of /. To test this, blood flow through IPAVAs was increased in healthy humans at rest breathing room air and 40% O2: (1) during intravenous adrenaline (epinephrine) infusion at 320 ng kg−1 min−1 (320 ADR), and (2) with vagal blockade (2 mg atropine), before and during intravenous adrenaline infusion at 80 ng kg−1 min−1 (ATR + 80 ADR). When breathing room air the A–aDO2 increased by 6 ± 2 mmHg during 320 ADR and by 5 ± 2 mmHg during ATR + 80 ADR, and the change in calculated / was +2% in both conditions. When breathing 40% O2, which minimizes contributions from diffusion limitation and alveolar ventilation‐to‐perfusion inequality, the A–aDO2 increased by 12 ± 7 mmHg during 320 ADR, and by 9 ± 6 mmHg during ATR + 80 ADR, and the change in calculated / was +2% in both conditions. During 320 ADR cardiac output () and pulmonary artery systolic pressure (PASP) were significantly increased; however, during ATR + 80 ADR only was significantly increased, yet blood flow through IPAVAs as detected with saline contrast echocardiography was not different between conditions. Accordingly, we suggest that blood flow through IPAVAs provides a source of intrapulmonary shunt, and is mediated primarily by increases in rather than PASP.
Direct inhibition of hypothalamic proopiomelanocortin neurons by dynorphin A is mediated by the μ‐opioid receptor
Authors: Pennock Reagan L. , Hentges Shane T. 
Published: August 2014

Key points
Dynorphin A inhibits anorexigenic hypothalamic proopiomelanocortin neurons by activating a potassium conductance.
Although dynorphin A is considered selective for κ‐opioid receptors, the present data show that the dynorphin A‐induced potassium conductance is reversed by a μ‐opioid receptor‐selective antagonist and is absent in mice lacking functional μ‐opioid receptors.
Thus, μ‐opioid receptors mediate the inhibition of proopiomelanocortin neurons caused by dynorphin A, consistent with other studies showing that κ‐opioid receptor‐selective agonists and antagonists can act at the μ‐opioid receptor when used at sufficiently high concentrations.
The results indicate that if dynorphin A inhibits proopiomelanocortin neurons to increase food intake, it does so either by activating μ‐opioid receptors on these neurons or by inhibiting κ‐opioid receptors located in the presynaptic compartment of proopiomelanocortin neurons.
AbstractIt has recently been shown that dynorphin A (Dyn A), an endogenous agonist of the κ‐opioid receptor (KOR), directly inhibits proopiomelanocortin (POMC) neurons in the hypothalamus through activation of G‐protein‐coupled inwardly rectifying K+ channels (GIRKs). This effect has been proposed to be mediated by the putative κ2‐opioid receptor (KOR‐2), and has been suggested as a possible mechanism for the orexigenic actions of KOR agonists. Using whole‐cell voltage clamp recordings in brain slice preparations, the present study demonstrates that Dyn A (1 or 5 μm) induces an outward current in POMC neurons that is reversed by the highly selective μ‐opioid receptor (MOR) antagonist CTAP and is absent in mice lacking MORs. Additionally, the KOR‐2‐selective agonist GR89696 binds MORs on POMC neurons but fails to induce an outward current. Similar to Dyn A, the KOR‐selective antagonist nor‐binaltorphimine (nor‐BNI) lacked specificity when used at sufficiently high concentrations. Maximal concentrations of the MOR‐selective agonist DAMGO induced outward currents in POMC neurons that were completely reversed by a relatively high concentration of nor‐BNI. Experiments using a half‐maximal concentration of DAMGO demonstrate that nor‐BNI must be used at concentrations <100 nm to avoid non‐specific actions of the antagonist at MORs located on POMC neurons. These data suggest that direct inhibition of POMC neurons by Dyn A is mediated through the MOR, not the KOR‐2, which is consistent with previous studies demonstrating that Dyn A can act at the μ‐opioid receptor (MOR) when present in high concentrations.
Fine spatiotemporal activity in contracting myometrium revealed by motion‐corrected calcium imaging
Authors: Loftus Fiona C. , Shmygol Anatoly , Richardson Magnus J. E. 
Published: August 2014

Key points
Calcium indicator fluorescence imaging is a key tool for investigating the physiological mechanisms that initiate and regulate myometrial contractions. However, inhomogeneous tissue motion severely limits the effective spatial resolution of measurable calcium activity.
We present an image analysis method that locally tracks contractions to produce a complete description of tissue‐wide motion. This renders calcium signals measurable at the micrometre scale. Additionally, the method simultaneously extracts kinematics of the motion that will inform biomechanical models of contracting myometrium.
The method is demonstrated on calcium‐imaging datasets of contracting myometrium. Using the method, we observed significant heterogeneity in calcium activity and identified a characteristic length scale of 40–50 μm below which tissue motion remains locally homogeneous.
We provide freely available and modifiable code to process datasets affected by motion artefacts. The method has potential application to in vivo neuron imaging, as well as to calcium imaging of other smooth muscle tissue.
AbstractSuccessful childbirth depends on the occurrence of precisely coordinated uterine contractions during labour. Calcium indicator fluorescence imaging is one of the main techniques for investigating the mechanisms governing this physiological process and its pathologies. The effective spatiotemporal resolution of calcium signals is, however, limited by the motion of contracting tissue: structures of interest in the order of microns can move over a hundred times their width during a contraction. The simultaneous changes in local intensity and tissue configuration make motion tracking a non‐trivial problem in image analysis and confound many of the standard techniques. This paper presents a method that tracks local motion throughout the tissue and allows for the almost complete removal of motion artefacts. This provides a stabilized calcium signal down to a pixel resolution, which, for the data examined, is in the order of a few microns. As a byproduct of image stabilization, a complete kinematic description of the contraction–relaxation cycle is also obtained. This contains novel information about the mechanical response of the tissue, such as the identification of a characteristic length scale, in the order of 40–50 μm, below which tissue motion is homogeneous. Applied to our data, we illustrate that the method allows for analyses of calcium dynamics in contracting myometrium in unprecedented spatiotemporal detail. Additionally, we use the kinematics of tissue motion to compare calcium signals at the subcellular level and local contractile motion. The computer code used is provided in a freely modifiable form and has potential applicability to in vivo calcium imaging of neural tissue, as well as other smooth muscle tissue.