Metformin improves ovarian function and increases egg production in broiler breeder hens.

In brief: The pathophysiology of the ovarian dysfunction encountered in broiler breeder hens remains poorly understood but is similar to a condition in women known as polycystic ovary syndrome. This study reveals that metformin may provide a cheap and effective method of improving ovarian function in broiler breeder hens. Abstract: Broiler breeder hens, the parent stock of commercial broiler chickens, have poor reproductive efficiency associated with aberrant and excessive recruitment of ovarian follicles which results in sub-optimal egg production, fertility, and hatchability. The reproductive dysfunction observed in these hens resembles polycystic ovary syndrome in women, a condition wherein metformin is prescribed as a treatment. The main objectives of this study were to determine the effect of metformin on body weight, abdominal fat pad weight, ovarian function, and plasma steroid hormone concentrations. Broiler breeder hens were treated with 0, 25, 50, or 75 mg/kg body weight of metformin mixed in the diet for 40 weeks (n = 45 hens/treatment; 2565 weeks of age). At 65 weeks of age, hens that received the highest dose of metformin had significantly lower body and abdominal fat pad weights (P < 0.05) than the control. Metformin treatment, at all levels, normalized the preovulatory and prehierarchical ovarian follicular hierarchy. Metformin (50 or 75 mg/kg body weight) significantly increased the total number of eggs laid per hen during the entire production period and these hens had significantly greater fertility and hatchability at 65 weeks of age compared to the control (P < 0.05). Metformin treatment at all levels altered the plasma profile of reproductive hormones, with significantly lower plasma testosterone concentrations and a decreased testosterone to androstenedione ratio in hens that received metformin (P < 0.05). Future studies should focus on the mechanisms underlying the beneficial effects of metformin in improving the reproductive efficiency of broiler breeder hens.

A perspective on the relative merits/demerits of time-propagators based on Floquet theorem.

The present report examines the nuances of analytic methods employed in the derivation of evolution operators in periodically driven quantum systems based on Floquet theorem. Specifically, time-propagators of the form, U(t) = P(t)e-iH̄t defined in the Hilbert space (of finite dimension), are derived through generalized multimodal expansion of the operators involved. While Floquet methods defined in the extended Hilbert space (of infinite dimension) have remained the method of choice for the description of time-evolution at non-stroboscopic time-intervals, the expansion schemes discussed do present an attractive option for similar studies in the standard Hilbert space. Nevertheless, the convergence criteria and suitability of such methods deserve formal validation in problems of experimental relevance. Employing examples comprising periodic Hamiltonians from magnetic resonance spectroscopy, the exactness of Floquet based time-propagators in the Schrödinger and interaction representation is discussed. Through rigorous comparisons between simulations emerging from analytic and exact numerical methods, the relative merits and demerits of different formulations of Floquet based methods are also discussed.

Quantifying quadrupole effects in the NMR spectra of spin-1/2 nuclei in rotating solids.

Quantifying the NMR spectra of spin I = 1/2 nuclei coupled to quadrupolar spins (nuclei with spin quantum number, S > 1/2) has remained an arduous task in solid-state magic angle spinning (MAS) NMR experiments. In particular, extraction of chemical shift anisotropy (CSA) tensors from line-shapes of spin I = 1/2 nuclei coupled to quadrupolar spin (S = 1) in MAS experiments has remained challenging owing to the simultaneous presence of both heteronuclear dipolar interactions and quadrupolar interactions. Unlike experiments that involve only spin-1/2 nuclei, both faster spinning frequencies and stronger decoupling field strengths on the quadrupolar spins are essential to average/minimize the contributions from heteronuclear dipolar interactions. To this end, a quantitative theory based on the concept of "effective fields" is proposed to deduce optimal conditions in experiments that involve simultaneous recoupling and decoupling of heteronuclear dipolar interactions. Through analytic expressions, the spectral frequencies and intensities observed in experiments are quantified and rigorously verified. Since extraction of molecular constraints in NMR experiments involves iterative fitting of experimental data, we believe that the analytic expressions derived would speed up and be beneficial in quantifying such experiments.

A critique on the suitability of Fer expansion in time-evolution studies in quantum mechanics.

The present report examines the utility and exactness of time-propagators derived from Fer expansion (FE). While the mathematical intricacies of the FE scheme are well established, the operational aspects of the same in time-evolution studies remain less explored and authenticated in physical problems of relevance. Through suitable examples, the operational inconsistencies observed in time-evolution studies based on the FE scheme are identified and corroborated through rigorous comparisons with simulations emerging from exact numerical methods. The limitations outlined seriously undermine the advantages associated with the FE scheme over other existing analytic methods.

Theory of radio-frequency pulses on periodically driven three-level systems: challenges and perspectives.

Understanding the evolution of nuclear spins subjected to radio-frequency (RF) pulses in periodically driven multi-level systems has remained a challenging problem in magnetic resonance. Here in this report, we focus on a formal description of the excitation of double-quantum (DQ) transitions in three-level systems. Through generalized time-propagators derived from Floquet theory, the excitation during a pulse at non-stroboscopic time intervals is analysed through expressions invoking the density operator formalism. In contrast to numerical simulations, the analytical expressions provide insights into the excitation phenomenon as well as facilitating the faster optimization of experiments and quantification of experimental data. Through rigorous comparison with simulations, the suitability and convergence criteria in the analytical methods are examined over a wide range of parameters (both internal and external) with appropriate examples.

Bimodal Floquet theory of phase-modulated heteronuclear decoupling experiments in solid-state NMR spectroscopy.

A prescription based on bimodal Floquet theory is proposed to describe the nuances of phase-modulated supercycled decoupling experiments in solids. The frequency dependent interaction frames relevant to a particular supercycle are identified to facilitate faster convergence of perturbation corrections to the derived effective Hamiltonians. In contrast to silico-based methods, the proposed analytic method offers an attractive platform for faster optimization of experiments in solids. Additionally, the relevance of supercycling at ultrafast spinning conditions is also discussed.

Evaluation of the Central Effects of Systemic Lentiviral-Mediated Leptin Delivery in Streptozotocin-Induced Diabetic Rats.

Type 1 diabetes (T1D) is characterized by hyperphagia, hyperglycemia and activation of the hypothalamic-pituitary-adrenal (HPA) axis. We have reported previously that daily leptin injections help to alleviate these symptoms. Therefore, we hypothesized that leptin gene therapy could help to normalize the neuroendocrine dysfunction seen in T1D. Adult male Sprague Dawley rats were injected i.v. with a lentiviral vector containing the leptin gene or green fluorescent protein. Ten days later, they were injected with the vehicle or streptozotocin (STZ). HPA function was assessed by measuring norepinephrine (NE) levels in the paraventricular nucleus (PVN) and serum corticosterone (CS). Treatment with the leptin lentiviral vector (Lepvv) increased leptin and insulin levels in non-diabetic rats, but not in diabetic animals. There was a significant reduction in blood glucose levels in diabetic rats due to Lepvv treatment. Both NE levels in the PVN and serum CS were reduced in diabetic rats treated with Lepvv. Results from this study provide evidence that leptin gene therapy in STZ-induced diabetic rats was able to partially normalize some of the neuroendocrine abnormalities, but studies with higher doses of the Lepvv are needed to develop this into a viable option for treating T1D.

Metformin attenuates steroidogenesis in ovarian follicles of the broiler breeder hen.

The follicular hierarchy in broiler breeder chicken ovary is often deranged due to excessive ovarian follicular recruitment, resulting in a condition that resembles polycystic ovary syndrome (PCOS) in women. Metformin is widely prescribed to correct PCOS and has been shown to affect granulosa cell functions in humans and rodent models. The objectives of this study are to determine the effects of metformin on signal transduction pathways, gene expression related to steroidogenesis, and progesterone secretion from granulosa cells isolated from the most recently recruited preovulatory and prehierarchical follicles of broiler breeder chickens. Granulosa cells were treated with 0, 1, 10, or 20 mM of metformin in the presence of FSH. The abundance of pAMPK, pACC, pERK, and pAkt was determined by Western blotting. The expression of genes related to progesterone biosynthesis was quantified by qPCR. Progesterone concentrations in culture media were quantified by ELISA. Metformin treatment did not have an effect on the abundance of pAMPK and pACC in prehierarchical follicles but significantly decreased the abundance of pERK and pAkt in a dose-dependent manner in preovulatory and prehierarchical follicles. The expression of genes related to steroidogenesis such as FSHR, STAR, CYP11A1, HSD3B, and progesterone secretion was significantly decreased in response to metformin treatment in a dose-dependent manner. Our data suggest that metformin treatment attenuates progesterone secretion via AMPK-independent pathways in granulosa cells of prehierarchical and preovulatory follicles of broiler breeder hens. Further studies are required to determine if metformin administration could ameliorate ovarian dysfunction in obese broiler breeder hens.

Adiponectin is secreted by theca layer cells isolated from chicken ovarian follicles.

Adiponectin, an adipokine hormone, influences glucose utilization, insulin sensitivity and energy homeostasis by signaling through two distinct receptors, ADIPOR1 and ADIPOR2. We previously reported that adiponectin and its receptors are expressed in several organs, including testes in chicken. We report herein that adiponectin gene is expressed exclusively in theca layer while ADIPOR1 and ADIPOR2 genes are expressed in granulosa and theca layers of all preovulatory and prehierarchical follicles of the chicken ovary. Estradiol and/or progesterone treatment of sexually immature chickens significantly altered expression of adiponectin and ADIPOR1 in the ovary. Using anti-chicken adiponectin-, ADIPOR1-, or ADIPOR2- antibodies, adiponectin-immunoreactive (ir) cells were found exclusively in the theca layer, and ADIPOR1-ir and ADIPOR2-ir cells were found both in theca and granulosa layers. Theca layer cells dispersed from preovulatory and prehierarchical follicles were found to synthesize and secrete a 720 kDa heavy molecular weight (HMW) isoform of adiponectin in vitro. Recombinant chicken adiponectin (rcADN) expressed in eukaryotic cells under serum-free conditions comprised primarily of the HMW isoform. Treatment of granulosa cells dispersed from 9 to 12 mm preovulatory follicle and 6 to 8 mm prehierarchical follicle with rcADN or an adiponectin receptor agonist, adipoRon, increased pERK and pACC abundance. In addition, both rcADN and adipoRon were found to significantly decrease the expression of steroidogenic acute regulatory protein gene expression in granulosa cells of preovulatory and prehierarchical follicles. In conclusion, adiponectin secreted by theca cell layer is identical in mass to circulating adiponectin. Systemic and/or theca-derived adiponectin is likely to affect proliferation, metabolism, and steroidogenesis of ovarian follicular cells.

A theoretical perspective on the suitability of bimodal Floquet theory in the description of heteronuclear decoupling in solids.

In this report, the suitability of bimodal Floquet theory in the description of heteronuclear decoupling experiments in solids is clarified under varied experimental conditions. Employing an operator equivalent of perturbation theory, a generalized framework for explicating the effects of multiple pulse schemes on internal spin interactions is described in the Floquet space. In contrast to in silico based methods, the analytic expressions derived from the present formalism yield faster results and offer better insights into the optimal conditions desired for maximizing the decoupling efficiency in experiments. Through appropriate examples, the validity of the approximations employed in the analytic theory is examined methodically through a comparison between analytic and numerical simulations.

Theory of coherent averaging in magnetic resonance using effective Hamiltonians.

A perturbative approach based on multimode Floquet theory is proposed to explain the coherent averaging effects of radio frequency pulses on nuclear spins in magnetic resonance experiments. Employing effective Hamiltonians, a uniform description of the time evolution of spins under arbitrary multiple pulse schemes is presented. The choice of interaction frames and transformation functions desired for faster convergence of the perturbation series is identified based on the experimental conditions. We believe that the methodology outlined would be beneficial in the design and optimization of experiments beyond existing strategies.

On the equivalence between different averaging schemes in magnetic resonance.

Evolution of quantum mechanical systems under time-dependent Hamiltonians has remained a challenging problem of interest across all disciplines. Through suitable approximations, different averaging methods have emerged in the past for modeling the time-evolution under time-dependent Hamiltonians. To this end, the development of analytic methods in the form of time-averaged effective Hamiltonians has gained prominence over other methods. In particular, the advancement of spectroscopic methods for probing molecular structures has benefited enormously from such theoretical pursuits. Nonetheless, the validity of the approximations and the exactness of the proposed effective Hamiltonians have always remained a contentious issue. Here, in this report, we reexamine the equivalence between the effective Hamiltonians derived from the Magnus formula and Floquet theory through suitable examples in magnetic resonance.

Effective Floquet Hamiltonian theory of multiple-quantum NMR in anisotropic solids involving quadrupolar spins: Challenges and Perspectives.

The response of a quadrupolar nucleus (nuclear spin with I >12) to an oscillating radio-frequency pulse/field is delicately dependent on the ratio of the quadrupolar coupling constant to the amplitude of the pulse in addition to its duration and oscillating frequency. Consequently, analytic description of the excitation process in the density operator formalism has remained less transparent within existing theoretical frameworks. As an alternative, the utility of the "concept of effective Floquet Hamiltonians" is explored in the present study to explicate the nuances of the excitation process in multilevel systems. Employing spin I =32 as a case study, a unified theoretical framework for describing the excitation of multiple-quantum transitions in static isotropic and anisotropic solids is proposed within the framework of perturbation theory. The challenges resulting from the anisotropic nature of the quadrupolar interactions are addressed within the effective Hamiltonian framework. The possible role of the various interaction frames on the convergence of the perturbation corrections is discussed along with a proposal for a "hybrid method" for describing the excitation process in anisotropic solids. Employing suitable model systems, the validity of the proposed hybrid method is substantiated through a rigorous comparison between simulations emerging from exact numerical and analytic methods.

Expression of adiponectin and its receptors is altered in epithelial ovarian tumors and ascites-derived ovarian cancer cell lines.

OBJECTIVES: Recent evidence suggests that higher body mass index is associated with a modest increase in ovarian cancer risk. Reduced serum levels of adiponectin are correlated with obesity and increased cancer risk. The objectives of the present study are to determine if expressions of adiponectin and its receptors, AdipoR1 and AdipoR2, are altered in epithelial ovarian tumors and ascites-derived ovarian cancer cell lines and to determine if plasma adiponectin levels are altered in the chicken model of ovarian cancer. METHODS: Adiponectin, AdipoR1, and AdipoR2 mRNA concentrations in ovaries and chicken ovarian cancer (COVCAR) cell lines were determined by quantitative real-time polymerase chain reaction analysis. Existence of adiponectin isoforms in the ovaries and COVCAR cells was identified by nondenaturing gel electrophoresis. Adiponectin, AdipoR1, and AdipoR2 protein amounts were determined by Western blot analysis. Plasma total adiponectin levels were determined by an enzyme immunoassay. RESULTS: Adiponectin, AdipoR1, and AdipoR2 mRNA concentrations were significantly lower in cancerous ovaries and COVCAR cell lines compared with normal ovaries and normal ovarian surface epithelial (NOSE) cells, respectively. Adiponectin in ovary and COVCAR cell lines appeared as a heavy-molecular-weight isoform that is greater than 720-kd mass. In addition, a lower-molecular-weight adiponectin isoform was found in COVCAR cells but not in NOSE cells. Adiponectin and AdipoR1 protein concentrations were not different in COVCAR cell lines compared with NOSE cells. However, AdipoR2 protein concentrations were significantly higher in cancerous ovaries but lower in COVCAR cell lines compared with normal ovaries and NOSE cells, respectively. Plasma adiponectin concentrations were not different in chickens that had ovarian carcinoma compared with control animals. CONCLUSIONS: Expression of adiponectin in ovarian tumors and in metastatic ovarian tumor cells is likely to affect cellular metabolism and proliferation through activating AdipoR1 and/or AdipoR2. Plasma adiponectin levels may not be predictive of advanced stages of ovarian tumor in the chicken model.

Unraveling multi-spin effects in rotational resonance nuclear magnetic resonance using effective reduced density matrix theory.

A quantum-mechanical model integrating the concepts of reduced density matrix and effective Hamiltonians is proposed to explain the multi-spin effects observed in rotational resonance (R(2)) nuclear magnetic resonance (NMR) experiments. Employing this approach, the spin system of interest is described in a reduced subspace inclusive of its coupling to the surroundings. Through suitable model systems, the utility of our theory is demonstrated and verified with simulations emerging from both analytic and numerical methods. The analytic results presented in this article provide an accurate description/interpretation of R(2) experimental results and could serve as a test-bed for distinguishing coherent/incoherent effects in solid-state NMR.

Current and future reproductive technologies for avian species.

The global demand for poultry meat and eggs is expected to increase exponentially in the next several decades. Increasing global poultry production in the future would require significant improvements in genetics, nutrition, and managerial practices including reproduction. This chapter summarizes some of the recent developments in ameliorating reproductive dysfunction in broiler breeder chickens, cryopreservation of avian spermatozoa, sex selection, and avian transgenesis.

Association between linear measurements of corpus callosum and gait in the elderly.

PURPOSE: Segmentation and diffusion-tensor-imaging of the corpus callosum (CC) have been linked to gait impairment. However, such measurements are impracticable in clinical routine. The purpose of this study was to evaluate the association between simple linear measurements of CC thickness with gait. METHODS: Two hundred and seventy-two community-dwelling subjects underwent neurological assessment and brain MRI. Mid-sagittal reformats of T1-weighted images were used to determine CC thickness. The association of measurements with clinical evaluation of gait was assessed by multivariate regression, controlling for numerous clinical and imaging confounders. Differences in CC thickness were, moreover, compared between subgroups with no, moderate or severe impairment of gait. RESULTS: In univariate analyses, thickness of the genu and body of CC but not the splenium were associated with postural stability (P < 0.01). Multivariate regression revealed thickness of CC genu as the only imaging variable independently associated with gait (P = 0.01). Genu thickness was significantly different between subjects with high and low (P = 0.0003) or high and moderate (P = 0.001) risk of fall. CONCLUSION: Atrophy of the CC genu is an imaging marker of gait impairment in the elderly suggesting higher risk of fall. Simple linear measurements of CC can help in MRI evaluation of patients with gait impairment. KEY POINTS: • Regional atrophy of the corpus callosum reflects disruption of gait regulation • Genu thickness on cranial MRI is an independent marker of gait impairment • Findings help in the MRI evaluation of patients with gait impairment.

Concept of effective Hamiltonians for transitions in multi-level systems.

Employing the concept of effective Hamiltonians, an analytical theory is introduced to describe transitions in a multi-level system in nuclear magnetic resonance (NMR) spectroscopy. Specifically, the discussion is centered towards the treatment of selective and non-selective excitations in static quadrupolar spin (I > 1/2) systems. To this end, effective radiofrequency (RF) Hamiltonians based on the spherical tensor formalism are proposed for describing transitions in both integral (I = 1, 2 and 3) and half-integral (I = 3/2, 5/2 and 7/2) quadrupolar spins. The optimum conditions desired for selective excitation in a multi-level system are derived pedagogically from first principles and presented through analytical expressions. Employing suitable model systems, the derived optimum conditions are substantiated through rigorous numerical simulations based on the spherical tensor formalism. The theory presented provides a framework for describing selective and non-selective RF pulses and could improve our understanding of multiple-pulse experiments involving quadrupolar nuclei.

Understanding multi-quantum NMR through secular approximation.

With the development of technology and improved understanding of nuclear spin-spin interactions and their behavior in static/oscillating magnetic fields, NMR spectroscopy has emerged as a powerful tool for characterizing molecular structure in a wide range of systems of chemical, physical and biological relevance. Here in this article, we revisit the important connection between "Secular-Approximation" (a well-known fundamental concept) and NMR spectroscopy. Employing recent experimental results as the background, an alternate interpretation of the secular approximation is presented for describing and understanding the nuances of Multi-Quantum (MQ) NMR spectroscopy of quadrupolar nuclei. Since MQ NMR spectroscopy of quadrupolar nuclei forms the basis of the structural characterization of inorganic solids and clusters, we believe that the analytic theory presented herein would be beneficial both in the understanding and design of MQ NMR experiments. Additionally, the analytic results are corroborated with rigorous numerical simulations and could be employed in the quantitative interpretation of experimental results.

Understanding cross-polarization (CP) NMR experiments through dipolar truncation.

A theoretical model based on the phenomenon of dipolar truncation is proposed to explain the nuances of polarization transfer from abundant to less-abundant nuclei in cross-polarization (CP) NMR experiments. Specifically, the transfer of polarization from protons to carbons (in solids) in strongly coupled systems is described in terms of effective Hamiltonians based on dipolar truncation. Through suitable model spin systems, the important role of dipolar truncation in the propagation of spin polarization in CP experiments is outlined. We believe that the analytic theory presented herein provides a convenient framework for modeling polarization transfer in strongly coupled systems.