AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons

Hypothalamic AMP-activated protein kinase (AMPK) has been suggested to act as a key sensing mechanism, responding to hormones and nutrients in the regulation of energy homeostasis. However, the precise neuronal populations and cellular mechanisms involved are unclear. The effects of long-term manipulation of hypothalamic AMPK on energy balance are also unknown. To directly address such issues, we generated POMC alpha 2KO and AgRP alpha 2KO mice lacking AMPK alpha 2 in proopiomelanocortin- (POMC-) and agouti-related protein-expressing (AgRP-expressing) neurons, key regulators of energy homeostasis. POMC alpha 2KO mice developed obesity due to reduced energy expenditure and dysregulated food intake but remained sensitive to leptin. in contrast, AgRPa2KO mice developed an age-dependent lean phenotype with increased sensitivity to a melanocortin agonist. Electrophysiological studies in AMPK alpha 2-deficient POMC or AgRP neurons revealed normal leptin or insulin action but absent responses to alterations in extracellular glucose levels, showing that glucose-sensing signaling mechanisms in these neurons are distinct from those pathways utilized by leptin or insulin. Taken together with the divergent phenotypes of POMC alpha 2KO and AgRP alpha 2KO mice, our findings suggest that while AMPK plays a key role in hypothalamic function, it does not act as a general sensor and integrator of energy homeostasis in the mediobasal hypothalamus

Non-linear response of a Kondo system: Perturbation approach to the time dependent Anderson impurity model

Nonlinear tunneling current through a quantum dot (an Anderson impurity system) subject to both constant and alternating electric fields is studied in the Kondo regime. A systematic diagram technique is developed for perturbation study of the current in physical systems out of equilibrium governed by time - dependent Hamiltonians of the Anderson and the Kondo models. The ensuing calculations prove to be too complicated for the Anderson model, and hence, a mapping on an effective Kondo problem is called for. This is achieved by constructing a time - dependent version of the Schrieffer - Wolff transformation. Perturbation expansion of the current is then carried out up to third order in the Kondo coupling J yielding a set of remarkably simple analytical expressions for the current. The zero - bias anomaly of the direct current differential conductance is shown to be suppressed by the alternating field while side peaks develop at finite source - drain voltage. Both the direct component and the first harmonics of the time - dependent response are equally enhanced due to the Kondo effect, while amplitudes of higher harmonics are shown to be relatively small. A zero alternating bias anomaly is found in the alternating current differential conductance, that is, it peaks around zero alternating bias. This peak is suppressed by the constant bias. No side peaks show up in the differential alternating - conductance but their counterpart is found in the derivative of the alternating current with respect to the direct bias. The results pertaining to nonlinear response are shown to be valid also below the Kondo temperature.Comment: 55 latex pages 11 ps figure

Heavy quarkonium: progress, puzzles, and opportunities

A golden age for heavy quarkonium physics dawned a decade ago, initiated by the confluence of exciting advances in quantum chromodynamics (QCD) and an explosion of related experimental activity. The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress. However, the broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles could only be partially anticipated. Since the release of the YR, the BESII program concluded only to give birth to BESIII; the $B$-factories and CLEO-c flourished; quarkonium production and polarization measurements at HERA and the Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the deconfinement regime. All these experiments leave legacies of quality, precision, and unsolved mysteries for quarkonium physics, and therefore beg for continuing investigations. The plethora of newly-found quarkonium-like states unleashed a flood of theoretical investigations into new forms of matter such as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b}, and b\bar{c} bound states have been shown to validate some theoretical approaches to QCD and highlight lack of quantitative success for others. The intriguing details of quarkonium suppression in heavy-ion collisions that have emerged from RHIC have elevated the importance of separating hot- and cold-nuclear-matter effects in quark-gluon plasma studies. This review systematically addresses all these matters and concludes by prioritizing directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K. Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D. Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A. Petrov, P. Robbe, A. Vair

Isomers in Pd128 and Pd126: Evidence for a Robust Shell Closure at the Neutron Magic Number 82 in Exotic Palladium Isotopes

The level structures of the very neutron-rich nuclei Pd128 and Pd126 have been investigated for the first time. In the r-process waiting-point nucleus Pd128, a new isomer with a half-life of 5.8(8) μs is proposed to have a spin and parity of 8+ and is a

Is American Public Administration Detached From Historical Context?: On the Nature of Time and the Need to Understand It in Government and Its Study

The study of public administration pays little attention to history. Most publications are focused on current problems (the present) and desired solutions (the future) and are concerned mainly with organizational structure (a substantive issue) and output targets (an aggregative issue that involves measures of both individual performance and organizational productivity/services). There is much less consideration of how public administration (i.e., organization, policy, the study, etc.) unfolds over time. History, and so administrative history, is regarded as a “past” that can be recorded for its own sake but has little relevance to contemporary challenges. This view of history is the product of a diminished and anemic sense of time, resulting from organizing the past as a series of events that inexorably lead up to the present in a linear fashion. To improve the understanding of government’s role and position in society, public administration scholarship needs to reacquaint itself with the nature of time.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

Recent advances in magnetic resonance microscopy to the physical structure characterization of carbonaceous and inorganic materials

Magnetic resonance microscopy (MRM) techniques have been employed to study the molecular architectures and properties of structural polymers, fossil fuels, microporous carbons and inorganic catalysts

Germplasm Evaluation Program Progress Report No. 22

Breeds with differences in performance characteristics are an important genetic resource for improving efficiency of beef production. Diverse breeds are required to exploit heterosis and breed complementarity through crossbreeding and development of Composite populations to match genetic potential with different markets, feed resources and climates. Beef producers are under increasing pressure to reduce fat while maintaining or improving tenderness and palatability of products. No single breed excels in all traits of economic importance to beef production. This report presents preliminary results from Cycle VII of the Germplasm Evaluation Program (GPE) at the Roman L. Hruska U.S. Meat Animal Research Center (U.S. Meat Animal Research Center) which focused on characterization of the seven Bos taurus breeds that register the largest number of animals in their respective herd books. Each breed, except Red Angus, had been characterized in earlier Cycles of the Germplasm Evaluation Program as shown in Table 1. The objective of Cycle VII was to evaluate relative changes in these breeds since they were evaluated with samples of sires born 25-30 years earlier and to provide a current evaluation of these prominent Bos taurus breeds