The selective functionalization of strong C−H bonds and the oxidation of water by cheap and nontoxic metals are some of the key targets of chemical research today. It has been proposed that ...high‐valent iron‐, manganese‐, and copper‐oxo cores are involved as reactive intermediates in important oxidation reactions performed by biological systems, thus making them attractive targets for biomimetic synthetic studies. The generation and characterization of metal–oxo model complexes of iron, manganese, and copper together with detailed reactivity studies can help in understanding how the steric and electronic properties of the metal centers modulate the reactivity of the metalloenzymes. This Review provides a focused overview of the advances in the chemistry of biomimetic high‐valent metal–oxo complexes from the last 5–10 years that can be related to our understanding of biological systems.
High‐valent Fe‐, Mn‐, and Cu‐oxo cores are proposed as reactive intermediates in biological oxidation reactions. The generation of well‐characterized model compounds can provide vital insights into the mechanisms of such enzymatic reactions. This Review provides a comprehensive summary of recent advances in biomimetic high‐valent metal–oxo complexes related to our understanding of biological systems.
Pancreaticoduodenectomy (PD) is considered the gold standard treatment for periampullory carcinomas. This procedure presents 30%-40% of morbidity. Patients who have undergone pancreaticoduodenectomy ...often present perioperative malnutrition that is worse in the early postoperative days, affects the process of healing, the intestinal barrier function and the number of postoperative complications. Few studies focus on the relation between enteral nutrition (EN) and postoperative complications. Our aim was to perform a review, including only randomized controlled trial meta-analyses or well-designed studies, of evidence regarding the correlation between EN and main complications and outcomes after pancreaticoduodenectomy, as delayed gastric emptying (DGE), postoperative pancreatic fistula (POPF), postpancreatectomy hemorrhage (PPH), length of stay and infectious complications. Several studies, especially randomized controlled trial have shown that EN does not increase the rate of DGE. EN appeared safe and tolerated for patients after PD, even if it did not reveal any advantages in terms of POPF, PPH, length of stay and infectious complications.
The emergence of plant hormone signaling pathways is deeply intertwined with land plant evolution. In angiosperms, two plant hormones, salicylic Acid (SA) and Jasmonates (JAs), play a key role in ...plant defense, where JAs-mediated defenses are typically activated in response to herbivores and necrotrophic pathogens, whereas SA is prioritized against hemi/biotrophic pathogens. Thus, studying the evolution of SA and JAs and their crosstalk is essential to understand the evolution of molecular plant–microbe interactions (EvoMPMI) in land plants. Recent advances in the evolution of SA and JAs biosynthesis, signaling, and crosstalk in land plants illustrated that the insight gained in angiosperms does not necessarily apply to non-seed plant lineages, where the receptors perceive different ligands and the hormones activate pathways independently on the canonical receptors. In this review, recent findings on the two main defense hormones (JAs and SA) in non-seed plants, including functional studies in the bryophyte model Marchantia polymorpha, will be discussed.
Alzheimer's disease AD is the most common cause of dementia in North America. Despite 30+ years of intense investigation, the field lacks consensus regarding the etiology and pathogenesis of sporadic ...AD, and therefore we still do not know the best strategies for treating and preventing this debilitating and costly disease. However, growing evidence supports the concept that AD is fundamentally a metabolic disease with substantial and progressive derangements in brain glucose utilization and responsiveness to insulin and insulin-like growth factor IGF stimulation. Moreover, AD is now recognized to be heterogeneous in nature, and not solely the end-product of aberrantly processed, misfolded, and aggregated oligomeric amyloid-beta peptides and hyperphosphorylated tau. Other factors, including impairments in energy metabolism, increased oxidative stress, inflammation, insulin and IGF resistance, and insulin/IGF deficiency in the brain should be incorporated into all equations used to develop diagnostic and therapeutic approaches to AD. Herein, the contributions of impaired insulin and IGF signaling to AD-associated neuronal loss, synaptic disconnection, tau hyperphosphorylation, amyloid-beta accumulation, and impaired energy metabolism are reviewed. In addition, we discuss current therapeutic strategies and suggest additional approaches based on the hypothesis that AD is principally a metabolic disease similar to diabetes mellitus. Ultimately, our ability to effectively detect, monitor, treat, and prevent AD will require more efficient, accurate and integrative diagnostic tools that utilize clinical, neuroimaging, biochemical, and molecular biomarker data. Finally, it is imperative that future therapeutic strategies for AD abandon the concept of uni-modal therapy in favor of multi-modal treatments that target distinct impairments at different levels within the brain insulin/IGF signaling cascades.
Growing evidence supports the concept that Alzheimer's disease (AD) is fundamentally a metabolic disease with molecular and biochemical features that correspond with diabetes mellitus and other ...peripheral insulin resistance disorders. Brain insulin/IGF resistance and its consequences can readily account for most of the structural and functional abnormalities in AD. However, disease pathogenesis is complicated by the fact that AD can occur as a separate disease process, or arise in association with systemic insulin resistance diseases, including diabetes, obesity, and non-alcoholic fatty liver disease. Whether primary or secondary in origin, brain insulin/IGF resistance initiates a cascade of neurodegeneration that is propagated by metabolic dysfunction, increased oxidative and ER stress, neuro-inflammation, impaired cell survival, and dysregulated lipid metabolism. These injurious processes compromise neuronal and glial functions, reduce neurotransmitter homeostasis, and cause toxic oligomeric pTau and (amyloid beta peptide of amyloid beta precursor protein) AβPP-Aβ fibrils and insoluble aggregates (neurofibrillary tangles and plaques) to accumulate in brain. AD progresses due to: (1) activation of a harmful positive feedback loop that progressively worsens the effects of insulin resistance; and (2) the formation of ROS- and RNS-related lipid, protein, and DNA adducts that permanently damage basic cellular and molecular functions. Epidemiologic data suggest that insulin resistance diseases, including AD, are exposure-related in etiology. Furthermore, experimental and lifestyle trend data suggest chronic low-level nitrosamine exposures are responsible. These concepts offer opportunities to discover and implement new treatments and devise preventive measures to conquer the AD and other insulin resistance disease epidemics.
Phytochrome-interacting factors (PIFs) are members of the Arabidopsis thaliana basic helix-loop-helix family of transcriptional regulators that interact specifically with the active Pfr conformer of ...phytochrome (phy) photoreceptors. PIFs are central regulators of photomorphogenic development that act to promote stem growth, and this activity is reversed upon interaction with phy in response to light. Recently, significant progress has been made in defining the transcriptional networks directly regulated by PIFs, as well as the convergence of other signaling pathways on the PIFs to modulate growth. Here, we summarize and highlight these findings in the context of PIFs acting as integrators of light and other signals. We discuss progress in our understanding of the transcriptional and posttranslational regulation of PIFs that illustrates the integration of light with hormonal pathways and the circadian clock, and we review seedling hypocotyl growth as a paradigm of PIFs acting at the interface of these signals. Based on these advances, PIFs are emerging as required factors for growth, acting as central components of a regulatory node that integrates multiple internal and external signals to optimize plant development.
Abstract
The primary objectives of forage-based livestock grazing systems are to enhance sustainability of pastures and cattle production, and to maintain economic stability in the presence of ...changes in input costs and returns. Grazing management strategies and implementation vary for adapted forages according to vegetational-hardiness zones, livestock production objectives, and manager preferences for grazing systems, stocking rates, and stocking methods. Stocking methods are strategies or techniques to manipulate grazing animals in space and time and may be considered as variations of continuous or rotational stocking. In many stocking method discussions, the debates are often focused on experimental confirmational data vs testimonials and perceptions. Acceptable methodology and statistical analyses of grazing experimentation on continuous vs rotational stocking provides repeated measures of forage nutritive value, forage mass, grazing intensity, and stocking rate on gain per animal, gain per unit land area. Additional measurements may include effects on forage stand maintenance and soil nutrient analyses-status. Recent adaptations of mob stocking and intensive rotational grazing via popular press and consultants have received acclaims for methods to enhance ecosystem services, soil health, and other non-experimentally documented attributes. Managers may adopt these testimonials of stocking methods of 60 days or more deferment based on their perception of protecting and enhancing the environment rather than logic of seeking experimental evidence. However, when given a choice of forage available for consumption, cattle select more than 80% of their diet as leaves. Thus, with respect to average daily gain per animal (ADG), only a small percentage of pasture studies have shown an advantage for rotational stocking. The lack of ADG was attributed to reduced nutritive value of forage available for selection during the residence time. Selecting management and stocking strategies for optimum utilization for forage produced, individual animal performance, and overall gain per unit land area has led to flexible grazing systems. These grazing systems may not be “hardcore rotationally, time-scheduled stocked,” but they do involve multiple pastures with strategies to incorporate movement of cattle based on current paddock forage status and forage mass estimates for desired animal performance. Grazing management strategies control the degree of intensity of beef cattle production based on level of economic risk and desired-expected environmental stewardship goals. Of all the strategies that management may adopt for grazing, the primary factor that controls resultant sustainability of pastures is that of grazing intensity as measured by stocking rate or forage height-density. Implementing revised or new management strategies requires attention to detail and the use of data-results-recommendations from comparative experiments conducted by a recognized source without conflict of interest in the method promoted.
Alzheimer's disease (AD) should be regarded as a degenerative metabolic disease caused by brain insulin resistance and deficiency, and overlapping with the molecular, biochemical, pathophysiological, ...and metabolic dysfunctions in diabetes mellitus, non-alcoholic fatty liver disease, and metabolic syndrome. Although most of the diagnostic and therapeutic approaches over the past several decades have focused on amyloid-beta (Aβ42) and aberrantly phosphorylated tau, which could be caused by consequences of brain insulin resistance, the broader array of pathologies including white matter atrophy with loss of myelinated fibrils and leukoaraiosis, non-Aβ42 microvascular disease, dysregulated lipid metabolism, mitochondrial dysfunction, astrocytic gliosis, neuro-inflammation, and loss of synapses vis-à-vis growth of dystrophic neurites, is not readily accounted for by Aβ42 accumulations, but could be explained by dysregulated insulin/IGF-1 signaling with attendant impairments in signal transduction and gene expression. This review covers the diverse range of brain abnormalities in AD and discusses how insulins, incretins, and insulin sensitizers could be utilized to treat at different stages of neurodegeneration.
PDF
