ALBERT

Description: Despite unequivocal evidence that folate deficiency increases risk for human pathologies, and that folic acid intake among women of childbearing age markedly decreases risk for birth defects, definitive evidence for a causal biochemical pathway linking folate to disease and birth defect etiology remains elusive. The de novo and salvage pathways for thymidylate synthesis translocate to the nucleus of mammalian cells during S- and G2/M-phases of the cell cycle and associate with the DNA replication and repair machinery, which limits uracil misincorporation into DNA and genome instability. There is increasing evidence that impairments in nuclear de novo thymidylate synthesis occur in many pathologies resulting from impairments in one-carbon metabolism. Understanding the roles and regulation of nuclear de novo thymidylate synthesis and its relationship to genome stability will increase our understanding of the fundamental mechanisms underlying folate- and vitamin B12–associated pathologies.

Description: The metabolic syndrome is a clustering of cardiovascular risk factors, including insulin resistance, abdominal obesity, dyslipidemia, and hypertension, and is associated with other comorbidities such as a proinflammatory state and nonalcoholic fatty liver disease (NAFLD). Its prevalence is high, especially among developed countries, and mainly reflects overnutrition and sedentary lifestyle. Moreover, the developing countries are not spared, as obesity and its related problems such as the metabolic syndrome are increasing quickly. We review the potential primary role of skeletal muscle insulin resistance in the pathophysiology of the metabolic syndrome, showing that in lean, young, insulin-resistant individuals, impaired muscle glucose transport and glycogen synthesis redirect energy derived from carbohydrate into hepatic de novo lipogenesis, promoting the development of atherogenic dyslipidemia and NAFLD. The demonstration of a link between skeletal muscle insulin resistance and the metabolic syndrome offers opportunities in targeting early defects in muscle insulin action in order to counteract the development of the disease and its related complications.

Description: MicroRNAs (miRNAs) represent an elegant mechanism of posttranscriptional control of gene expression that serves to fine-tune biological processes. These tiny noncoding RNAs (20–22 nucleotide) bind to the 3′ untranslated region of mRNAs, thereby repressing gene expression. Recent advances in the understanding of lipid metabolism have revealed that miRNAs, particularly miR-122 and miR-33, play major roles in regulating cholesterol and fatty acid homeostasis. miR-122, the most abundant miRNA in the liver, appears to maintain the hepatic cell phenotype, and its inhibition decreases total serum cholesterol. miR-33, an intronic miRNA located with the sterol response element-binding protein (SREBP)-2 gene, regulates cholesterol efflux, fatty acid β oxidation, and high-density lipoprotein metabolism. These findings have highlighted the complexity of lipid homeostasis and the important role that miRNAs play in these processes, potentially opening new avenues for the treatment of dyslipidemias.

Description: The circulation of nitrogen in nature is a prerequisite for life on earth. In the nitrogen cycle atmospheric nitrogen is fixated by bacteria into forms that can be utilized by plants and mammals. Nitrate and nitrite are obligate intermediates in this cycle, and for more than half a century these anions have interested nutritional scientists, mostly in relation to cancer, because of their ability to form nitrosamines. However, after the discovery of mammalian endogenous nitric oxide (NO) generation and later that its oxidation products nitrate and nitrite can be recycled back to bioactive NO, a novel field of research has emerged that explores a potentially beneficial role of these anions in physiology, nutrition, and therapeutics. In our diet, vegetables are the major source of nitrate that can fuel a nitrate-nitrite-NO pathway. Herein we discuss the nutritional aspects of this pathway and what is presently known about the implications for human health.

Description: The discovery by Dr. Constantine Londos of perilipin 1, the major scaffold protein at the surface of cytosolic lipid droplets in adipocytes, marked a fundamental conceptual change in the understanding of lipolytic regulation. Focus then shifted from the enzymatic activation of lipases to substrate accessibility, mediated by perilipin-dependent protein sequestration and recruitment. Consequently, the lipid droplet became recognized as a unique, metabolically active cellular organelle and its surface as the active site for novel protein–protein interactions. A new area of investigation emerged, centered on lipid droplets' biology and their role in energy homeostasis. The perilipin family is of ancient origin and has expanded to include five mammalian genes and a growing list of evolutionarily conserved members. Universally, the perilipins modulate cellular lipid storage. This review provides a summary that connects the perilipins to both cellular and whole-body homeostasis.

Description: Measures of B6 status are categorized as direct biomarkers and as functional biomarkers. Direct biomarkers measure B6 vitamers in plasma/serum, urine and erythrocytes, and among these plasma pyridoxal 5′-phosphate (PLP) is most commonly used. Functional biomarkers include erythrocyte transaminase activities and, more recently, plasma levels of metabolites involved in PLP-dependent reactions, such as the kynurenine pathway, one-carbon metabolism, transsulfuration (cystathionine), and glycine decarboxylation (serine and glycine). Vitamin B6 status is best assessed by using a combination of biomarkers because of the influence of potential confounders, such as inflammation, alkaline phosphatase activity, low serum albumin, renal function, and inorganic phosphate. Ratios between substrate-products pairs have recently been investigated as a strategy to attenuate such influence. These efforts have provided promising new markers such as the PAr index, the 3-hydroxykynurenine:xanthurenic acid ratio, and the oxoglutarate:glutamate ratio. Targeted metabolic profiling or untargeted metabolomics based on mass spectrometry allow the simultaneous quantification of a large number of metabolites, which are currently evaluated as functional biomarkers, using data reduction statistics.

Description: This review explores the multifaceted role that iron has in cancer biology. Epidemiological studies have demonstrated an association between excess iron and increased cancer incidence and risk, while experimental studies have implicated iron in cancer initiation, tumor growth, and metastasis. The roles of iron in proliferation, metabolism, and metastasis underpin the association of iron with tumor growth and progression. Cancer cells exhibit an iron-seeking phenotype achieved through dysregulation of iron metabolic proteins. These changes are mediated, at least in part, by oncogenes and tumor suppressors. The dependence of cancer cells on iron has implications in a number of cell death pathways, including ferroptosis, an iron-dependent form of cell death. Uniquely, both iron excess and iron depletion can be utilized in anticancer therapies. Investigating the efficacy of these therapeutic approaches is an area of active research that promises substantial clinical impact.

Description: Fatty acid regulation of hepatic gene transcription was first reported in the early 1990s. Several transcription factors have been identified as targets of fatty acid regulation. This regulation is achieved by direct fatty acid binding to the transcription factor or by indirect mechanisms where fatty acids regulate signaling pathways controlling the expression of transcription factors or the phosphorylation, ubiquitination, or proteolytic cleavage of the transcription factor. Although dietary fatty acids are well-established regulators of hepatic transcription factors, emerging evidence indicates that endogenously generated fatty acids are equally important in controlling transcription factors in the context of glucose and lipid homeostasis. Our first goal in this review is to provide an up-to-date examination of the molecular and metabolic bases of fatty acid regulation of key transcription factors controlling hepatic metabolism. Our second goal is to link these mechanisms to nonalcoholic fatty liver disease (NAFLD), a growing health concern in the obese population.

Description: Worldwide obesity rates have reached epidemic proportions and significantly contribute to the growing prevalence of metabolic diseases. Chronic low-grade inflammation, a hallmark of obesity, involves immune cell infiltration into expanding adipose tissue. In turn, obesity-associated inflammation can lead to complications in other metabolic tissues (e.g., liver, skeletal muscle, pancreas) through lipotoxicity and inflammatory signaling networks. Importantly, although numerous signaling pathways are known to integrate metabolic and inflammatory processes, the nucleotide-binding and oligomerization domain–like receptor, leucine-rich repeat and pyrin domain–containing 3 (NLRP3) inflammasome is now noted to be a key regulator of metabolic inflammation. The NLRP3 inflammasome can be influenced by various metabolites, including fatty acids. Specifically, although saturated fatty acids may promote NLRP3 inflammasome activation, monounsaturated fatty acids and polyunsaturated fatty acids have recently been shown to impede NLRP3 activity. Therefore, the NLRP3 inflammasome and associated metabolic inflammation have key roles in the relationships among fatty acids, metabolites, and metabolic disease. This review focuses on the ability of fatty acids to influence inflammation and the NLRP3 inflammasome across numerous metabolic tissues in the body. In addition, we explore some perspectives for the future, wherein recent work in the immunology field clearly demonstrates that metabolic reprogramming defines immune cell functionality. Although there is a paucity of information about how diet and fatty acids modulate this process, it is possible that this will open up a new avenue of research relating to nutrient-sensitive metabolic inflammation.

Description: Obesity and metabolic disease–related health problems (e.g., type 2 diabetes, atherosclerosis, and hypertension) are the most prevalent nutrition-related issues in the United States. An emerging feature of obesity and type 2 diabetes is their linkage with chronic inflammation that begins in white adipose tissue and eventually becomes systemic. One potential strategy to reduce inflammation and insulin resistance is consumption of polyphenol-rich foods like grapes or their by-products, which have anti-inflammatory properties. Polyphenols commonly found in grape products have been reported to reduce inflammation by (a) acting as an antioxidant or increasing antioxidant gene or protein expression, (b) attenuating endoplasmic reticulum stress signaling, (c) blocking proinflammatory cytokines or endotoxin-mediated kinases and transcription factors involved in metabolic disease, (d) suppressing inflammatory- or inducing metabolic-gene expression via increasing histone deacetylase activity, or (e) activating transcription factors that antagonize chronic inflammation. Thus, polyphenol-rich grape products may reduce obesity-mediated chronic inflammation by multiple mechanisms, thereby preventing metabolic diseases.

Description: This article summarizes current data and approaches to assess sodium intake in individuals and populations. A review of the literature on sodium excretion and intake estimation supports the continued use of 24-h urine collections for assessing population and individual sodium intake. Since 2000, 29 studies used urine biomarkers to estimate population sodium intake, primarily among adults. More than half used 24-h urine; the rest used a spot/casual, overnight, or 12-h specimen. Associations between individual sodium intake and health outcomes were investigated in 13 prospective cohort studies published since 2000. Only three included an indicator of long-term individual sodium intake, i.e., multiple 24-h urine specimens collected several days apart. Although not insurmountable, logistic challenges of 24-h urine collection remain a barrier for research on the relationship of sodium intake and chronic disease. Newer approaches, including modeling based on shorter collections, offer promise for estimating population sodium intake in some groups.

Description: In addition to providing complete postnatal nutrition, breast milk is a complex biofluid that delivers bioactive components for the growth and development of the intestinal and immune systems. Lactation is a unique opportunity to understand the role of diet in shaping the intestinal environment including the infant microbiome. Of considerable interest is the diversity and abundance of milk glycans that are energetically costly for the mammary gland to produce yet indigestible by infants. Milk glycans comprise free oligosaccharides, glycoproteins, glycopeptides, and glycolipids. Emerging technological advances are enabling more comprehensive, sensitive, and rapid analyses of these different classes of milk glycans. Understanding the impact of inter- and intraindividual glycan diversity on function is an important step toward interventions aimed at improving health and preventing disease. This review discusses the state of technology for glycan analysis and how specific structure-function knowledge is enhancing our understanding of early nutrition in the neonate.

Description: Mammary synthesis of milk fat continues to be an active research area, with significant advances in the regulation of lipid synthesis by bioactive fatty acids (FAs). The biohydrogenation theory established that diet-induced milk fat depression (MFD) in the dairy cow is caused by an inhibition of mammary synthesis of milk fat by specific FAs produced during ruminal biohydrogenation. The first such FA shown to affect milk fat synthesis was trans-10, cis-12 conjugated linoleic acid, and its effects have been well characterized, including dose-response relationships. During MFD, lipogenic capacity and transcription of key mammary lipogenic genes are coordinately down-regulated. Results provide strong evidence for sterol response element-binding protein-1 (SREBP1) and Spot 14 as biohydrogenation intermediate responsive lipogenic signaling pathway for ruminants and rodents. The study of MFD and its regulation by specific rumen-derived bioactive FAs represents a successful example of nutrigenomics in present-day animal nutrition research and offers several potential applications in animal agriculture.

Description: The synthesis of lipids in response to food intake represents a key advantage that allows organisms to survive when energy availability is limited. In mammals, circulating levels of insulin and nutrients, which fluctuate between fasting and feeding, dictate whether lipids are synthesized or catabolized by tissues. The mechanistic target of rapamycin (mTOR), a kinase that is activated by anabolic signals, plays fundamental roles in regulating lipid biosynthesis and metabolism in response to nutrition. The mTOR kinase nucleates two large protein complexes named mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Following their activation, these complexes facilitate the accumulation of triglycerides by promoting adipogenesis and lipogenesis and by shutting down catabolic processes such as lipolysis and β-oxidation. Here, we review and discuss the roles of mTOR complexes in various aspects of lipid metabolism in mammals. We also use this opportunity to discuss the implication of these relations to the maintenance of systemic lipid homeostasis.

Description: Various biotypes of endogenous small RNAs (sRNAs) have been detected in human circulation, including microRNAs, transfer RNAs, ribosomal RNA, and yRNA fragments. These extracellular sRNAs (ex-sRNAs) are packaged and secreted by many different cell types. Ex-sRNAs exhibit differences in abundance in several disease states and have, therefore, been proposed for use as effective biomarkers. Furthermore, exosome-borne ex-sRNAs have been reported to elicit physiological responses in acceptor cells. Exogenous ex-sRNAs derived from diet (most prominently from plants) and microorganisms have also been reported in human blood. Essential issues that remain to be conclusively addressed concern the (a) presence and sources of exogenous ex-sRNAs in human bodily fluids, (b) detection and measurement of ex-sRNAs in human circulation, (c) selectivity of ex-sRNA export and import, (d) sensitivity and specificity of ex-sRNA delivery to cellular targets, and (e) cell-, tissue-, organ-, and organism-wide impacts of ex-sRNA-mediated cell-to-cell communication. We survey the present state of knowledge of most of these issues in this review.

Description: We here discuss the role of brown adipose tissue on energy homeostasis and assess its potential as a target for body weight management. Because of their high number of mitochondria and the presence of uncoupling protein 1, brown fat adipocytes can be termed as energy inefficient for adenosine-5′-triphosphate (ATP) production but energy efficient for heat production. Thus, the energy inefficiency of ATP production, despite high energy substrate oxidation, allows brown adipose tissue to generate heat for body temperature regulation. Whether such thermogenic property also plays a role in body weight regulation is still debated. The recent (re)discovery of brown adipose tissue in human adults and a better understanding of brown adipose tissue development have encouraged the quest for new alternatives to treat obesity since obese individuals seem to have less brown adipose tissue mass/activity than do their lean counterparts. In this review, we discuss the physiological relevance of brown adipose tissue on thermogenesis and its potential usefulness on body weight control in humans.

Description: Dietary guidelines and recommendations, usually developed by government bodies or large authoritative organizations, have major downstream effects on public policy. A growing body of evidence supports the notion that there are serious deficiencies in the methods used to develop dietary guidelines. Such deficiencies include the failure to access or conduct comprehensive systematic reviews, a lack of systematic or rigorous evaluation of the quality of the evidence, a failure to acknowledge the limitations of the evidence base underlying recommendations, and insufficiently stringent management of conflicts of interest. These issues may be addressed by adhering to international standards for guideline development, including adopting systematic review methodology and using rigorous systems to evaluate the certainty of the evidence and to move from evidence to recommendations, of which the GRADE approach (Grading of Recommendations Assessment,Development and Evaluation) is the most rigorous and fully developed. Improving the methods by which dietary guidelines are produced has considerable potential to substantially improve public policy decision-making.

Description: Researchers hypothesize that pregnancy and lactation are part of a continuum, with lactation meant to “reset” the adverse metabolic profile that develops as a part of normal pregnancy, and that when lactation does not occur, women maintain an elevated risk of cardio-metabolic diseases. Several large prospective and retrospective studies, mostly from the United States and other industrialized countries, have examined the associations between lactation and cardio-metabolic outcomes. Less evidence exists regarding an association of lactation with maternal postpartum weight status and dyslipidemia, whereas more evidence exists for an association with diabetes, hypertension, and subclinical and clinical cardiovascular disease.

Description: The understanding of manganese (Mn) biology, in particular its cellular regulation and role in neurological disease, is an area of expanding interest. Mn is an essential micronutrient that is required for the activity of a diverse set of enzymatic proteins (e.g., arginase and glutamine synthase). Although necessary for life, Mn is toxic in excess. Thus, maintaining appropriate levels of intracellular Mn is critical. Unlike other essential metals, cell-level homeostatic mechanisms of Mn have not been identified. In this review, we discuss common forms of Mn exposure, absorption, and transport via regulated uptake/exchange at the gut and blood-brain barrier and via biliary excretion. We present the current understanding of cellular uptake and efflux as well as subcellular storage and transport of Mn. In addition, we highlight the Mn-dependent and Mn-responsive pathways implicated in the growing evidence of its role in Parkinson's disease and Huntington's disease. We conclude with suggestions for future focuses of Mn health-related research.

Description: The adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway arose early during evolution of eukaryotic cells, when it appears to have been involved in the response to glucose starvation and perhaps also in monitoring the output of the newly acquired mitochondria. Due to the advent of hormonal regulation of glucose homeostasis, glucose starvation is a less frequent event for mammalian cells than for single-celled eukaryotes. Nevertheless, the AMPK system has been preserved in mammals where, by monitoring cellular AMP:adenosine triphosphate (ATP) and adenosine diphosphate (ADP):ATP ratios and balancing the rates of catabolism and ATP consumption, it maintains energy homeostasis at a cell-autonomous level. In addition, hormones involved in maintaining energy balance at the whole-body level interact with AMPK in the hypothalamus. AMPK is activated by two widely used clinical drugs, metformin and aspirin, and also by many natural products of plants that are either derived from traditional medicines or are promoted as “nutraceuticals.”

Description: Fibroblast growth factor 21 (FGF21) is an endocrine hormone derived from the liver that exerts pleiotropic effects on the body to maintain overall metabolic homeostasis. During the past decade, there has been an enormous effort made to understand the physiological roles of FGF21 in regulating metabolism and to identify the mechanism for its potent pharmacological effects to reverse diabetes and obesity. Through both human and rodent studies, it is now evident that FGF21 levels are dynamically regulated by nutrient sensing, and consequently FGF21 functions as a critical regulator of nutrient homeostasis. In addition, recent studies using new genetic and molecular tools have provided critical insight into the actions of this endocrine factor. This review examines the numerous functions of FGF21 and highlights the therapeutic potential of FGF21-targeted pathways for treating metabolic disease.

Description: Tea, made from leaves of the plant Camellia sinensis, Theaceae, has been used by humans for thousands of years, first as a medicinal herb and then as a beverage that is consumed widely. For the past 25 years, tea has been studied extensively for its beneficial health effects, including prevention of cancer, reduction of body weight, alleviation of metabolic syndrome, prevention of cardiovascular diseases, and protection against neurodegenerative diseases. Whether these effects can be produced by tea at the levels commonly consumed by humans is an open question. This review examines these topics and elucidates the common mechanisms for these beneficial health effects. It also discusses other health effects and possible side effects of tea consumption. This article provides a critical assessment of the health effects of tea consumption and suggests new directions for research in this area.

Description: This review summarizes the current data on diabetes risk factors, prevalence, and prevention efforts in Asia and Asian migrant populations. Studies indicate that type 2 diabetes mellitus is a large and growing threat to public health in Asian populations. Furthermore, Asian subgroups (e.g., South Asians/Asian Indians, Chinese) have unique risk factor profiles for developing diabetes, which differ from other populations and between Asian ethnic groups. Lifestyle intervention programs are effective in preventing diabetes in Asians, as with other ethnicities. The strength of these findings is lessened by the lack of systematically collected data using objective measurements. Large epidemiologic studies of diabetes prevalence and risk factor profiles and translational trials identifying sustainable and culturally acceptable lifestyle programs for Asian subgroups are needed.

Description: Each of the macronutrients—carbohydrate, protein, and fat—has a unique set of properties that influences health, but all are a source of energy. The optimal balance of their contribution to the diet has been a long-standing matter of debate. Over the past half century, thinking has progressed regarding the mechanisms by which each macronutrient may contribute to energy balance. At the beginning of this period, metabolic signals that initiated eating events (i.e., determined eating frequency) were emphasized. This was followed by an orientation to gut endocrine signals that purportedly modulate the size of eating events (i.e., determined portion size). Most recently, research attention has been directed to the brain, where the reward signals elicited by the macronutrients are viewed as potentially problematic (e.g., contribute to disordered eating). At this point, the predictive power of the macronutrients for energy intake remains limited.

Description: Long-chain omega-3 fatty acids belong to a family of polyunsaturated fatty acids that are known to have important beneficial effects on metabolism and inflammation. Such effects may confer a benefit in specific chronic noncommunicable diseases that are becoming very prevalent in Westernized societies [e.g., nonalcoholic fatty liver disease (NAFLD)]. Typically, with a Westernized diet, long-chain omega-6 fatty acid consumption is markedly greater than omega-3 fatty acid consumption. The potential consequences of an alteration in the ratio of omega-6 to omega-3 fatty acid consumption are increased production of proinflammatory arachidonic acid–derived eicosanoids and impaired regulation of hepatic and adipose function, predisposing to NAFLD. NAFLD represents a spectrum of liver fat–related conditions that originates with ectopic fat accumulation in liver (hepatic steatosis) and progresses, with the development of hepatic inflammation and fibrosis, to nonalcoholic steatohepatitis (NASH). If the adipose tissue is inflamed with widespread macrophage infiltration, the production of adipokines may act to exacerbate liver inflammation and NASH. Omega-3 fatty acid treatment may have beneficial effects in regulating hepatic lipid metabolism, adipose tissue function, and inflammation. Recent studies testing the effects of omega-3 fatty acids in NAFLD are showing promise and suggesting that these fatty acids may be useful in the treatment of NAFLD. To date, further research is needed in NAFLD to (a) establish the dose of long-chain omega-3 fatty acids as a treatment, (b) determine the duration of therapy, and (c) test whether there is benefit on the different component features of NAFLD (hepatic fat, inflammation, and fibrosis).

Description: With obesity affecting approximately 12.5 million American youth, population-level interventions are indicated to help support healthy behaviors. The purpose of this review is to provide a summary of population-level intervention strategies and specific intervention examples that illustrate ways to help prevent and control obesity in children through improving nutrition and physical activity behaviors. Information is summarized within the settings where children live, learn, and play (early care and education, school, community, health care, home). Intervention strategies are activities or changes intended to promote healthful behaviors in children. They were identified from (a) systematic reviews; (b) evidence- and expert consensus–based recommendations, guidelines, or standards from nongovernmental or federal agencies; and finally (c) peer-reviewed synthesis reviews. Intervention examples illustrate how at least one of the strategies was used in a particular setting. To identify interventions examples, we considered (a) peer-reviewed literature as well as (b) additional sources with research-tested and practice-based initiatives. Researchers and practitioners may use this review as they set priorities and promote integration across settings and to find research- and practice-tested intervention examples that can be replicated in their communities for childhood obesity prevention.

Description: The underlying causes of nonalcoholic fatty liver disease are unclear, although recent evidence has implicated the endoplasmic reticulum in both the development of steatosis and progression to nonalcoholic steatohepatitis. Disruption of endoplasmic reticulum homeostasis, often termed ER stress, has been observed in liver and adipose tissue of humans with nonalcoholic fatty liver disease and/or obesity. Importantly, the signaling pathway activated by disruption of endoplasmic reticulum homeostasis, the unfolded protein response, has been linked to lipid and membrane biosynthesis, insulin action, inflammation, and apoptosis. Therefore, understanding the mechanisms that disrupt endoplasmic reticulum homeostasis in nonalcoholic fatty liver disease and the role of the unfolded protein response in the broader context of chronic, metabolic diseases have become topics of intense investigation. The present review examines the endoplasmic reticulum and the unfolded protein response in the context of nonalcoholic fatty liver disease.

Description: Focusing on daily nutrition is important for athletes to perform and adapt optimally to exercise training. The major roles of an athlete's daily diet are to supply the substrates needed to cover the energy demands for exercise, to ensure quick recovery between exercise bouts, to optimize adaptations to exercise training, and to stay healthy. The major energy substrates for exercising skeletal muscles are carbohydrate and fat stores. Optimizing the timing and type of energy intake and the amount of dietary macronutrients is essential to ensure peak training and competition performance, and these strategies play important roles in modulating skeletal muscle adaptations to endurance and resistance training. In this review, recent advances in nutritional strategies designed to optimize exercise-induced adaptations in skeletal muscle are discussed, with an emphasis on mechanistic approaches, by describing the physiological mechanisms that provide the basis for different nutrition regimens.

Description: Plasma levels of triacylglycerols and diacylglycerols, the lipoproteins that transport them, and proteins involved in their absorption from the intestinal lumen fluctuate in a circadian manner. These changes are likely controlled by clock genes expressed in the intestine that are probably synchronized by neuronal and humoral signals from the suprachiasmatic nuclei, which constitute a master clock entrained by light signals from the eyes and from the environment, e.g., food availability. Acute changes in circadian rhythms—e.g., due to nonsynchronous work schedules or a transcontinental flight—may trigger intestinal discomfort. Chronic disruptions in circadian control mechanisms may predispose the individual to irritable bowel syndrome, gastroesophageal reflux disease, and peptic ulcer disease. A more detailed understanding of the molecular mechanisms underlying temporal changes in intestinal activity might allow us to identify novel targets for developing therapeutic approaches to these disorders.

Description: Liver glucose metabolism is dependent on glucokinase activity. Glucokinase expression is transcriptionally regulated by hormones and metabolites of glucose, and glucokinase activity is dependent on reversible binding of glucokinase to a specific inhibitor protein, glucokinase regulatory protein (GKRP), and to other binding proteins such as 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase (PFK2/FBP2), which functions as an activator. Glucokinase is inhibited in the postabsorptive state by sequestration in the nucleus bound to GKRP, and it is activated postprandially by portal hyperglycemia and fructose through dissociation from GKRP, translocation to the cytoplasm, and binding to PFK2/FBP2. Glucagon dissociates this interaction, promoting translocation back to the nucleus. In humans, changes in glucokinase expression and activity are associated with poorly controlled type 2 diabetes and with nonalcoholic fatty liver disease, and a common variant of GKRP with altered binding affinity for glucokinase is associated with increased blood and liver lipids and other metabolic traits that implicate a role for GKRP in maintaining intrahepatic metabolite homeostasis.

Description: Deposition of fat in the fetus increases exponentially with gestational age, reaching its maximal rate—around 7 g/day or 90% of energy deposition—at term. In late pregnancy, many women consuming contemporary Western diets may not be able to meet the fetal demand for n-3 long chain polyunsaturated fatty acids (LCPUFAs) from the diet alone. Numerous mechanisms have evolved to protect human offspring from extreme variation or deficiency in the maternal diet during pregnancy. Maternal adipose tissue is an important source of LCPUFA. Temporal changes in placental function are synchronized with maternal metabolic and physiological changes to ensure a continuous supply of n-3 and n-6 LCPUFA-enriched fat to the fetus. LCPUFA storage in fetal adipose tissue provides an important source of LCPUFA during the critical first months of postnatal life. An appreciation of these adaptations is important in any nutritional strategy designed to improve the availability of fatty acids to the fetus.

Description: Although obesity is a well-known risk factor for several cancers, its role on cancer survival is poorly understood. We conducted a systematic literature review to assess the current evidence evaluating the impact of body adiposity on the prognosis of the three most common obesity-related cancers: prostate, colorectal, and breast. We included 33 studies of breast cancer, six studies of prostate cancer, and eight studies of colo-rectal cancer. We note that the evidence overrepresents breast cancer survivorship research and is sparse for prostate and colorectal cancers. Overall, most studies support a relationship between body adiposity and site-specific mortality or cancer progression. However, most of the research was not specifically designed to study these outcomes and, therefore, several methodological issues should be considered before integrating their results to draw conclusions. Further research is urgently warranted to assess the long-term impact of obesity among the growing population of cancer survivors.

Description: e- and m-Health communication technologies are now common approaches to improving population health. The efficacy of behavioral nutrition interventions using e-health technologies to decrease fat intake and increase fruit and vegetable intake was demonstrated in studies conducted from 2005 to 2009, with approximately 75% of trials showing positive effects. By 2010, an increasing number of behavioral nutrition interventions were focusing on body weight. The early emphasis on interventions that were highly computer tailored shifted to personalized electronic interventions that included weight and behavioral self-monitoring as key features. More diverse target audiences began to participate, and mobile components were added to interventions. Little progress has been made on using objective measures rather than self-reported measures of dietary behavior. A challenge for nutritionists is to link with the private sector in the design, use, and evaluation of the many electronic devices that are now available in the marketplace for nutrition monitoring and behavioral change.

Description: Visfatin/NAMPT (nicotinamide phosphoribosyltransferase) is a protein with several suggested functions. Although the first discovery of this molecule as a pre-B-cell colony-enhancing factor suggested primarily a cytokine function, its rediscovery as the key enzyme in nicotinamide adenine dinucleotide generation has considerably widened its potential biological activities. Although originally thought to be produced in adipose tissue (i.e., adipocytes and infiltrating macrophages), its production seems to involve other cells and tissues such as skeletal muscle, liver, immune cells, cardiomyocytes, and the brain. Visfatin/NAMPT has both intracellular and extracellular effects influencing several signaling pathways. Its broad spectrum of effects is mirrored by its potential involvement in a wide range of disorders including human immunodeficiency virus infection, septicemia, myocardial failure, atherosclerosis, metabolic disorders, inflammatory diseases, malignancies, and neurodegenerative disorders and aging. Moreover, studies on visfatin/NAMPT in atherosclerotic disorders suggest a rather complex role of this molecule in pathophysiology, potentially mediating both adaptive and maladaptive responses.

Description: Maternal adaptations during pregnancy and lactation appear to provide calcium to fetus and neonate without relying on vitamin D or calcitriol. Consequently, the blood calcium, calciotropic hormones, and skeleton appear normal at birth in the offspring of mothers who are severely vitamin D deficient or who lack calcitriol or its receptor. It remains unclear whether skeletal or extraskeletal problems will develop postnatally from exposure to vitamin D deficiency in utero. During the neonatal period, calcitriol-stimulated intestinal calcium absorption becomes the dominant mechanism of calcium delivery. The vitamin D–deficient neonate is at risk to develop hypocalcemia, rickets, and possibly extraskeletal disorders (e.g., type 1 diabetes). Breastfed babies are at higher risk of vitamin D deficiency because normally little vitamin D or 25-hydroxyvitamin D passes into breast milk. Dosing recommendations during pregnancy and lactation should ensure that the baby is born vitamin D sufficient and maintained that way during infancy and beyond.

Description: The mammalian target of rapamycin (mTOR) pathway coordinates cell growth in response to nutrient availability. Increasing evidence points to a role for mTOR to also direct whole-body energy balance in response to micronutrient as well as hormonal cues. This positions mTOR as a key central integrator of acute and chronic changes in fuel status. Energy balance is affected by mTOR in several organ systems, including the hypothalamus, where the pathway can modulate feeding. We propose that a greater understanding of this nutrient-sensitive pathway may open the door to more intelligent, effective diet design based on the effects of micronutrients on specific signaling pathways.

Description: A wide spectrum of human diseases, including cancer, neurodegenerative diseases, and metabolic disorders, have been shown to be associated with mitochondrial dysfunction through multiple molecular mechanisms. Mitochondria are particularly susceptible to nutrient deficiencies, and nutritional intervention is an essential way to maintain mitochondrial homeostasis. Recent advances in genetic manipulation and next-generation sequencing reveal the crucial roles of mitochondrial DNA (mtDNA) in various pathophysiological conditions. Mitophagy, a term coined to describe autophagy that targets dysfunctional mitochondria, has emerged as an important cellular process to maintain mitochondrial homeostasis and has been shown to be regulated by various nutrients and nutritional stresses. Given the high prevalence of mtDNA mutations in humans and their impact on mitochondrial function, it is important to investigate the mechanisms that regulate mtDNA mutation. Here, we discuss mitochondrial genetics and mtDNA mutations and their implications for human diseases. We also examine the role of mitophagy as a therapeutic target, highlighting how nutrients may eliminate mtDNA mutations through mitophagy.

Description: The ability of adipose tissue to adapt to a changing nutrient environment is critical to the maintenance of metabolic control. Nutrient excess and deficiency alter the shape of adipose tissue drastically and trigger many events that are collectively known as adipose tissue remodeling. Remodeling of adipose tissue involves more than adipocytes and is controlled by an extensive network of stromal cells and extracellular matrix proteins. Prominent players in this process are adipose tissue macrophages, which are a specialized leukocyte present in lean and obese states that contributes to adipose tissue inflammation. The interest in adipose tissue remodeling has been accelerated by the current epidemic of obesity and the chronic generation of signals that lead to expansion of adipose tissue. It is clear that evidence of dysfunctional remodeling events is a hallmark of obesity associated with metabolic disease. This review summarizes and highlights the recent work in this area and provides a framework in which to consider how adipose tissue macrophages contribute to the remodeling events in lean and obese states. Advancing our understanding of the involvement of macrophages in adipose tissue remodeling will promote one aspect of the new field of “immunometabolism,” which connects control systems developed for regulation of immunity with those that control metabolism. It will also provide insight into how physiologic and pathophysiologic remodeling differs in adipose tissue and identify potential nodes for intervention to break the link between obesity and disease.

Description: Endophytes are microorganisms that live within plant tissues without causing symptoms of disease. They are important components of plant microbiomes. Endophytes interact with, and overlap in function with, other core microbial groups that colonize plant tissues, e.g., mycorrhizal fungi, pathogens, epiphytes, and saprotrophs. Some fungal endophytes affect plant growth and plant responses to pathogens, herbivores, and environmental change; others produce useful or interesting secondary metabolites. Here, we focus on new techniques and approaches that can provide an integrative understanding of the role of fungal endophytes in the plant microbiome. Clavicipitaceous endophytes of grasses are not considered because they have unique properties distinct from other endophytes. Hidden from view and often overlooked, endophytes are emerging as their diversity, importance for plant growth and survival, and interactions with other organisms are revealed.

Description: Predisposition results from abiotic stresses occurring prior to infection that affect susceptibility of plants to disease. The environment is seldom optimal for plant growth, and even mild, episodic stresses can predispose plants to inoculum levels they would otherwise resist. Plant responses that are adaptive in the short term may conflict with those for resisting pathogens. Abiotic and biotic stress responses are coordinated by complex signaling networks involving phytohormones and reactive oxygen species (ROS). Abscisic acid (ABA) is a global regulator in stress response networks and an important phytohormone in plant-microbe interactions with systemic effects on resistance and susceptibility. However, extensive cross talk occurs among all the phytohormones during stress events, and the challenge is discerning those interactions that most influence disease. Identifying convergent points in the stress response circuitry is critically important in terms of understanding the fundamental biology that underscores the disease phenotype as well as translating research to improve stress tolerance and disease management in production systems.

Description: Symbiotic nitrogen-fixing rhizobium bacteria and arbuscular mycorrhizal fungi use lipochitooligosaccharide (LCO) signals to communicate with potential host plants. Upon a compatible match, an intimate relation is established during which the microsymbiont is allowed to enter root (-derived) cells. Plants perceive microbial LCO molecules by specific LysM-domain-containing receptor-like kinases. These do not only activate a common symbiosis signaling pathway that is shared in both symbioses but also modulate innate immune responses. Recent studies revealed that symbiotic LCO receptors are closely related to chitin innate immune receptors, and some of these receptors even function in symbiosis as well as immunity. This raises questions about how plants manage to translate structurally very similar microbial signals into different outputs. Here, we describe the current view on chitin and LCO perception in innate immunity and endosymbiosis and question how LCOs might modulate the immune system. Furthermore, we discuss what it takes to become an endosymbiont.

Description: Genetically engineered crops have been grown for more than 20 years, resulting in widespread albeit variable benefits for farmers and consumers. We review current, likely, and potential genetic engineering (GE) applications for the development of disease-resistant crop cultivars. Gene editing, gene drives, and synthetic biology offer novel opportunities to control viral, bacterial, and fungal pathogens, parasitic weeds, and insect vectors of plant pathogens. We conclude that there will be no shortage of GE applications to tackle disease resistance and other farmer and consumer priorities for agricultural crops. Beyond reviewing scientific prospects for genetically engineered crops, we address the social institutional forces that are commonly overlooked by biological scientists. Intellectual property regimes, technology regulatory frameworks, the balance of funding between public- and private-sector research, and advocacy by concerned civil society groups interact to define who uses which GE technologies, on which crops, and for the benefit of whom. Ensuring equitable access to the benefits of genetically engineered crops requires affirmative policies, targeted investments, and excellent science.

Description: Huanglongbing (HLB) is the most destructive citrus pathosystem worldwide. Previously known primarily from Asia and Africa, it was introduced into the Western Hemisphere in 2004. All infected commercial citrus industries continue to decline owing to inadequate current control methods. HLB increase and regional spatial spread, related to vector populations, are rapid compared with other arboreal pathosystems. Disease dynamics result from multiple simultaneous spatial processes, suggesting that psyllid vector transmission is a continuum from local area to very long distance. Evolutionarily, HLB appears to have originated as an insect endosymbiont that has moved into plants. Lack of exposure of citrus to the pathogen prior to approximately 100 years ago did not provide sufficient time for development of resistance. A prolonged incubation period and regional dispersal make eradication nonviable. Multiple asymptomatic infections per symptomatic tree, incomplete systemic distribution within trees, and prolonged incubation period make detection difficult and greatly complicate disease control.

Description: Parasitic plants steal sugars, water, and other nutrients from host plants through a haustorial connection. Several species of parasitic plants such as witchweeds ( Striga spp.) and broomrapes ( Orobanche and Phelipanche spp.) are major biotic constraints to agricultural production. Parasitic plants are understudied compared with other major classes of plant pathogens, but the recent availability of genomic and transcriptomic data has accelerated the rate of discovery of the molecular mechanisms underpinning plant parasitism. Here, we review the current body of knowledge of how parasitic plants sense host plants, germinate, form parasitic haustorial connections, and suppress host plant immune responses. Additionally, we assess whether parasitic plants fit within the current paradigms used to understand the molecular mechanisms of microbial plant–pathogen interactions. Finally, we discuss challenges facing parasitic plant research and propose the most urgent questions that need to be answered to advance our understanding of plant parasitism.

Description: As primary producers, plants are under constant pressure to defend themselves against potentially deadly pathogens and herbivores. In this review, we describe short- and long-term strategies that enable plants to cope with these stresses. Apart from internal immunological strategies that involve physiological and (epi)genetic modifications at the cellular level, plants also employ external strategies that rely on recruitment of beneficial organisms. We discuss these strategies along a gradient of increasing timescales, ranging from rapid immune responses that are initiated within seconds to (epi)genetic adaptations that occur over multiple plant generations. We cover the latest insights into the mechanistic and evolutionary underpinnings of these strategies and present explanatory models. Finally, we discuss how knowledge from short-lived model species can be translated to economically and ecologically important perennials to exploit adaptive plant strategies and mitigate future impacts of pests and diseases in an increasingly interconnected and changing world.

Description: Soft-rot Enterobacteriaceae (SRE), which belong to the genera Pectobacterium and Dickeya, consist mainly of broad host-range pathogens that cause wilt, rot, and blackleg diseases on a wide range of plants. They are found in plants, insects, soil, and water in agricultural regions worldwide. SRE encode all six known protein secretion systems present in gram-negative bacteria, and these systems are involved in attacking host plants and competing bacteria. They also produce and detect multiple types of small molecules to coordinate pathogenesis, modify the plant environment, attack competing microbes, and perhaps to attract insect vectors. This review integrates new information about the role protein secretion and detection and production of ions and small molecules play in soft-rot pathogenicity.

Description: Many living organisms on Earth have evolved the ability to integrate environmental and internal signals to determine time and thereafter adjust appropriately their metabolism, physiology, and behavior. The circadian clock is the endogenous timekeeper critical for multiple biological processes in many organisms. A growing body of evidence supports the importance of the circadian clock for plant health. Plants activate timed defense with various strategies to anticipate daily attacks of pathogens and pests and to modulate responses to specific invaders in a time-of-day-dependent manner (gating). Pathogen infection is also known to reciprocally modulate clock activity. Such a cross talk likely reflects the adaptive nature of plants to coordinate limited resources for growth, development, and defense. This review summarizes recent progress in circadian regulation of plant innate immunity with a focus on the molecular events linking the circadian clock and defense. More and better knowledge of clock-defense cross talk could help to improve disease resistance and productivity in economically important crops.

Description: To confer resistance against pathogens and pests in plants, typically dominant resistance genes are deployed. However, because resistance is based on recognition of a single pathogen-derived molecular pattern, these narrow-spectrum genes are usually readily overcome. Disease arises from a compatible interaction between plant and pathogen. Hence, altering a plant gene that critically facilitates compatibility could provide a more broad-spectrum and durable type of resistance. Here, such susceptibility (S) genes are reviewed with a focus on the mechanisms underlying loss of compatibility. We distinguish three groups of S genes acting during different stages of infection: early pathogen establishment, modulation of host defenses, and pathogen sustenance. The many examples reviewed here show that S genes have the potential to be used in resistance breeding. However, because S genes have a function other than being a compatibility factor for the pathogen, the side effects caused by their mutation demands a one-by-one assessment of their usefulness for application.

Description: Crop pests and pathogens (CPPs) present a growing threat to food security and ecosystem management. The interactions between plants and their natural enemies are influenced by environmental conditions and thus global warming and climate change could affect CPP ranges and impact. Observations of changing CPP distributions over the twentieth century suggest that growing agricultural production and trade have been most important in disseminating CPPs, but there is some evidence for a latitudinal bias in range shifts that indicates a global warming signal. Species distribution models using climatic variables as drivers suggest that ranges will shift latitudinally in the future. The rapid spread of the Colorado potato beetle across Eurasia illustrates the importance of evolutionary adaptation, host distribution, and migration patterns in affecting the predictions of climate-based species distribution models. Understanding species range shifts in the framework of ecological niche theory may help to direct future research needs.

Description: Producers worldwide need access to the best plant varieties and cultivars available to be competitive in global markets. This often means moving plants across international borders as soon as they are available. At the same time, quarantine agencies are tasked with minimizing the risk of introducing exotic pests and pathogens along with imported plant material, with the goal to protect domestic agriculture and native fauna and flora. These two drivers, the movement of more plant material and reduced risk of pathogen introduction, are at odds. Improvements in large-scale or next-generation sequencing (NGS) and bioinformatics for data analysis have resulted in improved speed and accuracy of pathogen detection that could facilitate plant trade with reduced risk of pathogen movement. There are concerns to be addressed before NGS can replace existing tools used for pathogen detection in plant quarantine and certification programs. Here, we discuss the advantages and possible pitfalls of this technology for meeting the needs of plant quarantine and certification.

Description: Various conceptual models to describe the plant immune system have been presented. The most recent paradigm to gain wide acceptance in the field is often referred to as the zigzag model, which reconciles the previously formulated gene-for-gene hypothesis with the recognition of general elicitors in a single model. This review focuses on the limitations of the current paradigm of molecular plant-microbe interactions and how it too narrowly defines the plant immune system. As such, we discuss an alternative view of plant innate immunity as a system that evolves to detect invasion. This view accommodates the range from mutualistic to parasitic symbioses that plants form with diverse organisms, as well as the spectrum of ligands that the plant immune system perceives. Finally, how this view can contribute to the current practice of resistance breeding is discussed.

Description: Plants possess large arsenals of immune receptors capable of recognizing all pathogen classes. To cause disease, pathogenic organisms must be able to overcome physical barriers, suppress or evade immune perception, and derive nutrients from host tissues. Consequently, to facilitate some of these processes, pathogens secrete effector proteins that promote colonization. This review covers recent advances in the field of effector biology, focusing on conserved cellular processes targeted by effectors from diverse pathogens. The ability of effectors to facilitate pathogen entry into the host interior, suppress plant immune perception, and alter host physiology for pathogen benefit is discussed. Pathogens also deploy effectors in a spatial and temporal manner, depending on infection stage. Recent advances have also enhanced our understanding of effectors acting in specific plant organs and tissues. Effectors are excellent cellular probes that facilitate insight into biological processes as well as key points of vulnerability in plant immune signaling networks.

Description: Molecular pathology of forest trees for a long time lagged behind parallel studies on agricultural crop pathology. Recent technological advances have significantly contributed to the observed progress in this field. The first powerful impulse was provided by the completion of the black cottonwood genome sequence in 2006. Genomes of several other important tree species will be completed within a short time. Simultaneously, application of transcriptomics and next-generation sequencing (NGS) has resulted in the rapid accumulation of a vast amount of data on molecular interactions between trees and their microbial parasites. This review provides an overview of our current knowledge about these responses of forest trees to their pathogens, highlighting the achievements of the past decade, discussing the current state of the field, and emphasizing the prospects and challenges for the near future.

Description: Until recently, most studies on the role of hormones in plant-pathogen interactions focused on salicylic acid (SA), jasmonic acid (JA), and ethylene (ET). It is now clear that pathogen-induced modulation of signaling via other hormones contributes to virulence. A picture is emerging of complex crosstalk and induced hormonal changes that modulate disease and resistance, with outcomes dependent on pathogen lifestyles and the genetic constitution of the host. Recent progress has revealed intriguing similarities between hormone signaling mechanisms, with gene induction responses often achieved by derepression. Here, we report on recent advances, updating current knowledge on classical defense hormones SA, JA, and ET, and the roles of auxin, abscisic acid (ABA), cytokinins (CKs), and brassinosteroids in molding plant-pathogen interactions. We highlight an emerging theme that positive and negative regulators of these disparate hormone signaling pathways are crucial regulatory targets of hormonal crosstalk in disease and defense.

Description: Race Ug99 of the fungus Puccinia graminis tritici that causes stem or black rust disease on wheat was first detected in Uganda in 1998. Seven races belonging to the Ug99 lineage are now known and have spread to various wheat-growing countries in the eastern African highlands, as well as Zimbabwe, South Africa, Sudan, Yemen, and Iran. Because of the susceptibility of 90% of the wheat varieties grown worldwide, the Ug99 group of races was recognized as a major threat to wheat production and food security. Its spread, either wind-mediated or human-aided, to other countries in Africa, Asia, and beyond is evident. Screening in Kenya and Ethiopia has identified a low frequency of resistant wheat varieties and breeding materials. Identification and transfer of new sources of race-specific resistance from various wheat relatives is underway to enhance the diversity of resistance. Although new Ug99-resistant varieties that yield more than current popular varieties are being released and promoted, major efforts are required to displace current Ug99 susceptible varieties with varieties that have diverse race-specific or durable resistance and mitigate the Ug99 threat.

Description: Studies with model plants such as Arabidopsis thaliana have revealed that phytohormones are central regulators of plant defense. The intricate network of phytohormone signaling pathways enables plants to activate appropriate and effective defense responses against pathogens as well as to balance defense and growth. The timing of the evolution of most phytohormone signaling pathways seems to coincide with the colonization of land, a likely requirement for plant adaptations to the more variable terrestrial environments, which included the presence of pathogens. In this review, we explore the evolution of defense hormone signaling networks by combining the model plant-based knowledge about molecular components mediating phytohormone signaling and cross talk with available genome information of other plant species. We highlight conserved hubs in hormone cross talk and discuss evolutionary advantages of defense hormone cross talk. Finally, we examine possibilities of engineering hormone cross talk for improvement of plant fitness and crop production.

Description: Replant disease of apple is common to all major apple growing regions of the world. Difficulties in defining disease etiology, which can be exacerbated by abiotic factors, have limited progress toward developing alternatives to soil fumigation for disease control. However, the preponderance of data derived from studies of orchard soil biology employing multidisciplinary approaches has defined a complex of pathogens/parasites as causal agents of the disease. Approaches to manipulate microbial resources endemic to the orchard soil system have been proposed to induce a state of general soil suppressiveness to replant disease. Such a long-term strategy may benefit the existing orchard through extending the period of economic viability and reduce overall disease pressure to which young trees are exposed during establishment of successive plantings on the site. Alternatively, more near-term methods have been devised to achieve specific quantitative and qualitative changes in soil biology during the period of orchard renovation that may lead to effective disease suppression.

Description: The first section presents the quantitative traits of pathogenicity that are most commonly measured by plant pathologists, how the expression of those traits is influenced by environmental factors, and why the traits must be taken into account for understanding pathogen evolution in agricultural systems. Particular attention is given to the shared genetic control of these traits by the host and the pathogen. Next, the review discusses how quantitative traits account for epidemic development and how they can be related to pathogen fitness. The main constraints that influence the evolution of quantitative traits in pathogen populations are detailed. Finally, possible directions for research on the management of pathogen virulence (as defined by evolutionists) and host quantitative resistance are presented. The review evaluates how the theoretical corpus developed by epidemiologists and evolutionists may apply to plant pathogens in the context of agriculture. The review also analyzes theoretical papers and compares the modeling hypotheses to the biological characteristics of plant pathogens.

Description: A never-ending arms race drives coevolution between pathogens and hosts. In plants, pathogen attacks invoke multiple layers of host immune responses. Many pathogens deliver effector proteins into host cells to suppress host immunity, and many plants have evolved resistance proteins to recognize effectors and trigger robust resistance. Here, we discuss findings on noncoding small RNAs (sRNAs) from plants and pathogens, which regulate host immunity and pathogen virulence. Recent discoveries have unveiled the role of noncoding sRNAs from eukaryotic pathogens and bacteria in pathogenicity in both plant and animal hosts. The discovery of fungal sRNAs that are delivered into host cells to suppress plant immunity added sRNAs to the list of pathogen effectors. Similar to protein effector genes, many of these sRNAs are generated from transposable element (TE) regions, which are likely to contribute to rapidly evolving virulence and host adaptation. We also discuss RNA silencing that occurs between organisms.

Description: Soil- and plant-associated environments harbor numerous bacteria that produce antibiotic metabolites with specific or broad-spectrum activities against coexisting microorganisms. The function and ecological importance of antibiotics have long been assumed to yield a survival advantage to the producing bacteria in the highly competitive but resource-limited soil environments through direct suppression. Although specific antibiotics may enhance producer persistence when challenged by competitors or predators in soil habitats, at subinhibitory concentrations antibiotics exhibit a diversity of other roles in the life history of the producing bacteria. Many processes modulated by antibiotics may be inherently critical to the producing bacterium, such as the acquisition of substrates or initiation of developmental changes that will ensure survival under stressful conditions. Antibiotics may also have roles in more complex interactions, including in virulence on host plants or in shaping the outcomes of multitrophic interactions. The innate functions of antibiotics to producing bacteria in their native ecosystem are just beginning to emerge, but current knowledge already reveals a breadth of activities well beyond the historical perspective of antibiotics as weaponry in microbial conflicts.

Description: Studies on resistance gene function and evolution lie at the confluence of structural and molecular biology, genetics, and plant breeding. However, knowledge from these disparate fields has yet to be extensively integrated. This review draws on ideas and information from these different fields to elucidate the influences driving the evolution of different types of resistance genes in plants and the concurrent evolution of virulence in pathogens. It provides an overview of the factors shaping the evolution of recognition, signaling, and response genes in the context of emerging functional information along with a consideration of the new opportunities for durable resistance enabled by high-throughput DNA sequencing technologies.

Description: Breeding for disease resistance is a central focus of plant breeding programs, as any successful variety must have the complete package of high yield, disease resistance, agronomic performance, and end-use quality. With the need to accelerate the development of improved varieties, genomics-assisted breeding is becoming an important tool in breeding programs. With marker-assisted selection, there has been success in breeding for disease resistance; however, much of this work and research has focused on identifying, mapping, and selecting for major resistance genes that tend to be highly effective but vulnerable to breakdown with rapid changes in pathogen races. In contrast, breeding for minor-gene quantitative resistance tends to produce more durable varieties but is a more challenging breeding objective. As the genetic architecture of resistance shifts from single major R genes to a diffused architecture of many minor genes, the best approach for molecular breeding will shift from marker-assisted selection to genomic selection. Genomics-assisted breeding for quantitative resistance will therefore necessitate whole-genome prediction models and selection methodology as implemented for classical complex traits such as yield. Here, we examine multiple case studies testing whole-genome prediction models and genomic selection for disease resistance. In general, whole-genome models for disease resistance can produce prediction accuracy suitable for application in breeding. These models also largely outperform multiple linear regression as would be applied in marker-assisted selection. With the implementation of genomic selection for yield and other agronomic traits, whole-genome marker profiles will be available for the entire set of breeding lines, enabling genomic selection for disease at no additional direct cost. In this context, the scope of implementing genomics selection for disease resistance, and specifically for quantitative resistance and quarantined pathogens, becomes a tractable and powerful approach in breeding programs.

Description: Decision-support systems (DSSs) are interactive computer-based systems that help decision makers solve unstructured problems under complex, uncertain conditions. Experimental use of DSSs has resulted in improved disease suppression and lowered risks of crop damage. In many cases, it has also led to the use of smaller quantities of active substances, as compared with standard spraying practices. Hundreds of DSSs have been developed over the years and are readily available and affordable. However, most farm managers do not use them as part of their integrated pest management (IPM) practices. Since the mid-1980s, the author of this paper, together with numerous colleagues, has developed DSSs and decision rules for the management of diseases in a variety of crops, including extensive crops, such as wheat, sunflower, and pea; semi-intensive crops, such as pear, chickpea, cotton, and tarragon; and intensive crops, such as tomato, potato, cucumber, sweet pepper, carrot, and grapevine. Some of these systems were used widely, but others were not. This experience may allow us to draw general conclusions regarding the use of DSSs and decision rules. Possible explanations for the widely varying acceptance rates are presented, and the effects of anticipated changes in the agribusiness sector on the future use of DSSs are discussed.

Description: Beneficial microbes in the microbiome of plant roots improve plant health. Induced systemic resistance (ISR) emerged as an important mechanism by which selected plant growth–promoting bacteria and fungi in the rhizosphere prime the whole plant body for enhanced defense against a broad range of pathogens and insect herbivores. A wide variety of root-associated mutualists, including Pseudomonas, Bacillus, Trichoderma, and mycorrhiza species sensitize the plant immune system for enhanced defense without directly activating costly defenses. This review focuses on molecular processes at the interface between plant roots and ISR-eliciting mutualists, and on the progress in our understanding of ISR signaling and systemic defense priming. The central role of the root-specific transcription factor MYB72 in the onset of ISR and the role of phytohormones and defense regulatory proteins in the expression of ISR in aboveground plant parts are highlighted. Finally, the ecological function of ISR-inducing microbes in the root microbiome is discussed.

Description: The innate immune system of plants recognizes microbial pathogens and terminates their growth. However, recent findings suggest that at least one layer of this system is also engaged in cooperative plant-microbe interactions and influences host colonization by beneficial microbial communities. This immune layer involves sensing of microbe-associated molecular patterns (MAMPs) by pattern recognition receptors (PRRs) that initiate quantitative immune responses to control host-microbial load, whereas diversification of MAMPs and PRRs emerges as a mechanism that locally sculpts microbial assemblages in plant populations. This suggests a more complex microbial management role of the innate immune system for controlled accommodation of beneficial microbes and in pathogen elimination. The finding that similar molecular strategies are deployed by symbionts and pathogens to dampen immune responses is consistent with this hypothesis but implies different selective pressures on the immune system due to contrasting outcomes on plant fitness. The reciprocal interplay between microbiota and the immune system likely plays a critical role in shaping beneficial plant-microbiota combinations and maintaining microbial homeostasis.

Description: “Candidatus Liberibacter” species are associated with economically devastating diseases of citrus, potato, and many other crops. The importance of these diseases as well as the proliferation of new diseases on a wider host range is likely to increase as the insects vectoring the “Ca. Liberibacter” species expand their territories worldwide. Here, we review the progress on understanding pathogenesis mechanisms of “Ca. Liberibacter” species and the control approaches for diseases they cause. We discuss the Liberibacter virulence traits, including secretion systems, putative effectors, and lipopolysaccharides (LPSs), as well as other important traits likely to contribute to disease development, e.g., flagella, prophages, and salicylic acid hydroxylase. The pathogenesis mechanisms of Liberibacters are discussed. Liberibacters secrete Sec-dependent effectors (SDEs) or other virulence factors into the phloem elements or companion cells to interfere with host targets (e.g., proteins or genes), which cause cell death, necrosis, or other phenotypes of phloem elements or companion cells, leading to localized cell responses and systemic malfunction of phloem. Receptors on the remaining organelles in the phloem, such as plastid, vacuole, mitochondrion, or endoplasmic reticulum, interact with secreted SDEs and/or other virulence factors secreted or located on the Liberibacter outer membrane to trigger cell responses. Some of the host genes or proteins targeted by SDEs or other virulence factors of Liberibacters serve as susceptibility genes that facilitate compatibility (e.g., promoting pathogen growth or suppressing immune responses) or disease development. In addition, Liberibacters trigger plant immunity response via pathogen-associated molecular patterns (PAMPs, such as lipopolysaccharides), which leads to premature cell death, callose deposition, or phloem protein accumulation, causing a localized response and/or systemic effect on phloem transportation. Physical presence of Liberibacters and their metabolic activities may disturb the function of phloem, via disrupting osmotic gradients, or the integrity of phloem conductivity. We also review disease management strategies, including promising new technologies. Citrus production in the presence of Huanglongbing is possible if the most promising management approaches are integrated. HLB management is discussed in the context of local, area-wide, and regional Huanglongbing/Asian Citrus Psyllid epidemiological zones. For zebra chip disease control, aggressive psyllid management enables potato production, although insecticide resistance is becoming an issue. Meanwhile, new technologies such as clustered regularly interspaced short palindromic repeat (CRISPR)-derived genome editing provide an unprecedented opportunity to provide long-term solutions.

Description: Heterobasidion annosum sensu lato is a species complex comprising five species that are widely distributed in coniferous forests of the Northern Hemisphere and are each characterized by a distinct host preference. More than 1,700 papers have been published on these fungi in the past four decades, making them perhaps the most widely studied forest fungi. Heterobasidion species are at different levels on the saprotroph-necrotroph gradient, and the same individual can switch from one mode to the other. This offers a unique opportunity to study how genomic structure, gene expression, and genetic trade-offs may all interact with environmental factors to determine the life mode of the organism. The abilities of Heterobasidion spp. to infect stumps as saprotrophs and to spread to neighboring trees as pathogens have resulted in significant damages to timber production in managed forests. This review focuses on the current knowledge of the biology, ecology, evolution, and management of these species and is based on classical and modern studies.

Description: Twenty years ago, breakthroughs for reverse genetics analyses of negative-strand RNA (NSR) viruses were achieved by devising conditions for generation of infectious viruses in susceptible cells. Recombinant strategies have subsequently been engineered for members of all vertebrate NSR virus families, and research arising from these advances has profoundly increased understanding of infection cycles, pathogenesis, and complexities of host interactions of animal NSR viruses. These strategies also permitted development of many applications, including attenuated vaccines and delivery vehicles for therapeutic and biotechnology proteins. However, for a variety of reasons, it was difficult to devise procedures for reverse genetics analyses of plant NSR viruses. In this review, we discuss advances that have circumvented these problems and resulted in construction of a recombinant system for Sonchus yellow net nucleorhabdovirus. We also discuss possible extensions to other plant NSR viruses as well as the applications that may emanate from recombinant analyses of these pathogens.

Description: How pathogens coevolve with and adapt to their hosts are critical to understanding how host jumps and/or acquisition of novel traits can lead to new disease emergences. The Xanthomonas genus includes Gram-negative plant-pathogenic bacteria that collectively infect a broad range of crops and wild plant species. However, individual Xanthomonas strains usually cause disease on only a few plant species and are highly adapted to their hosts, making them pertinent models to study host specificity. This review summarizes our current understanding of the molecular basis of host specificity in the Xanthomonas genus, with a particular focus on the ecology, physiology, and pathogenicity of the bacterium. Despite our limited understanding of the basis of host specificity, type III effectors, microbe-associated molecular patterns, lipopolysaccharides, transcriptional regulators, and chemotactic sensors emerge as key determinants for shaping host specificity.

Description: Tobacco mosaic virus and other tobamoviruses have served as models for studying the mechanisms of viral RNA replication. In tobamoviruses, genomic RNA replication occurs via several steps: (a) synthesis of viral replication proteins by translation of the genomic RNA; (b) translation-coupled binding of the replication proteins to a 5′-terminal region of the genomic RNA; (c) recruitment of the genomic RNA by replication proteins onto membranes and formation of a complex with host proteins TOM1 and ARL8; (d) synthesis of complementary (negative-strand) RNA in the complex; and (e) synthesis of progeny genomic RNA. This article reviews current knowledge on tobamovirus RNA replication, particularly regarding how the genomic RNA is specifically selected as a replication template and how the replication proteins are activated. We also focus on the roles of the replication proteins in evading or suppressing host defense systems.

Description: Colonization of plants by particular endophytic fungi can provide plants with improved defenses toward nematodes. Evidently, such endophytes can be important in developing more sustainable agricultural practices. The mechanisms playing a role in this quantitative antagonism are poorly understood but most likely multifactorial. This knowledge gap obstructs the progress regarding the development of endophytes or endophyte-derived constituents into biocontrol agents. In part, this may be caused by the fact that endophytic fungi form a rather heterogeneous group. By combining the knowledge of the currently characterized antagonistic endophytic fungi and their effects on nematode behavior and biology with the knowledge of microbial competition and induced plant defenses, the various mechanisms by which this nematode antagonism operates or may operate are discussed. Now that new technologies are becoming available and more accessible, the currently unresolved mechanisms can be studied in greater detail than ever before.

Description: Many plants, both in nature and in agriculture, are resistant to multiple diseases. Although much of the plant innate immunity system provides highly specific resistance, there is emerging evidence to support the hypothesis that some components of plant defense are relatively nonspecific, providing multiple disease resistance (MDR). Understanding MDR is of fundamental and practical interest to plant biologists, pathologists, and breeders. This review takes stock of the available evidence related to the MDR hypothesis. Questions about MDR are considered primarily through the lens of forward genetics, starting at the organismal level and proceeding to the locus level and, finally, to the gene level. At the organismal level, MDR may be controlled by clusters of R genes that evolve under diversifying selection, by dispersed, pathogen-specific genes, and/or by individual genes providing MDR. Based on the few MDR loci that are well-understood, MDR is conditioned by diverse mechanisms at the locus and gene levels.

Description: Rice reoviruses, transmitted by leafhopper or planthopper vectors in a persistent propagative manner, seriously threaten the stability of rice production in Asia. Understanding the mechanisms that enable viral transmission by insect vectors is a key to controlling these viral diseases. This review describes current understanding of replication cycles of rice reoviruses in vector cell lines, transmission barriers, and molecular determinants of vector competence and persistent infection. Despite recent breakthroughs, such as the discoveries of actin-based tubule motility exploited by viruses to overcome transmission barriers and mutually beneficial relationships between viruses and bacterial symbionts, there are still many gaps in our knowledge of transmission mechanisms. Advances in genome sequencing, reverse genetics systems, and molecular technologies will help to address these problems. Investigating the multiple interaction systems among the virus, insect vector, insect symbiont, and plant during natural infection in the field is a central topic for future research on rice reoviruses.

Description: Plant disease arises from the interaction of processes occurring at multiple spatial and temporal scales. With new tools such as next-generation sequencing, we are learning about the diversity of microbes circulating within and among plant populations and often coinhabiting host individuals. The proliferation of pathogenic microbes depends on single-species dynamics and multispecies interactions occurring within and among host cells, the spatial organization and genetic landscape of hosts, the frequency and mode of transmission among hosts and host populations, and the abiotic environmental context. Here, we examine empirical evidence from these multiple scales to assess the utility of metacommunity theory, a theoretical framework developed for free-living organisms to further our understanding of and assist in predicting plant-pathogen infection and spread. We suggest that deeper understanding of disease dynamics can arise through the application of this conceptual framework at scales ranging from individual cells to landscapes. In addition, we use this multiscale theoretical perspective to synthesize existing knowledge, generate novel hypotheses, and point toward promising future opportunities for the study of plant pathogens in natural populations.

Description: During the past three decades, the economic impact of tospoviruses has increased, causing high yield losses in a variety of crops and ornamentals. Owing to the difficulty in combating thrips vectors with insecticides, the best way to limit/prevent tospovirus-induced diseases involves a management strategy that includes virus resistance. This review briefly presents current tospovirus taxonomy, diversity, molecular biology, and cytopathology as an introduction to a more extensive description of the two main resistance genes employed against tospoviruses: the Sw5 gene in tomato and the Tsw in pepper. Natural and experimental resistance-breaking (RB) isolates allowed the identification of the viral avirulence protein triggering each of the two resistance gene products; epidemiology of RB isolates is discussed to reinforce the need for allelic variants and the need to search for new/alternative resistance genes. Ongoing efforts for alternative resistance strategies are described not only for Tomato spotted wilt virus (TSWV) in pepper and tomato but also for other vegetable crops heavily impacted by tospoviruses.

Description: Systems biology attempts to answer biological questions by integrating across diverse genomic data sets. With the increasing ability to conduct genomics experiments, this integrative approach is being rapidly applied across numerous biological research communities. One of these research communities investigates how plants utilize secondary metabolites or defense metabolites to defend against attack by pathogens and other biotic organisms. This use of systems biology to integrate across transcriptomics, metabolomics, and genomics is significantly enhancing the rate of discovery of genes, metabolites, and bioactivities for plant defense compounds as well as extending our knowledge of how these compounds are regulated. Plant defense compounds are also providing a unique proving platform to develop new approaches that enhance the ability to conduct systems biology with existing and previously unforseen genomics data sets. This review attempts to illustrate both how systems biology is helping the study of plant defense compounds and vice versa.

Description: Virus diseases that have emerged in the past two decades limit the production of important vegetable crops in tropical, subtropical, and temperate regions worldwide, and many of the causal viruses are transmitted by whiteflies (order Hemiptera, family Aleyrodidae). Most of these whitefly-transmitted viruses are begomoviruses (family Geminiviridae), although whiteflies are also vectors of criniviruses, ipomoviruses, torradoviruses, and some carlaviruses. Factors driving the emergence and establishment of whitefly-transmitted diseases include genetic changes in the virus through mutation and recombination, changes in the vector populations coupled with polyphagy of the main vector, Bemisia tabaci, and long distance traffic of plant material or vector insects due to trade of vegetables and ornamental plants. The role of humans in increasing the emergence of virus diseases is obvious, and the effect that climate change may have in the future is unclear.

Description: Aspergillus flavus is saprophytic soil fungus that infects and contaminates preharvest and postharvest seed crops with the carcinogenic secondary metabolite aflatoxin. The fungus is also an opportunistic animal and human pathogen causing aspergillosis diseases with incidence increasing in the immunocompromised population. Whole genome sequences of A. flavus have been released and reveal 55 secondary metabolite clusters that are regulated by different environmental regimes and the global secondary metabolite regulators LaeA and VeA. Characteristics of A. flavus associated with pathogenicity and niche specialization include secondary metabolite production, enzyme elaboration, and a sophisticated oxylipin host crosstalk associated with a quorum-like development program. One of the more promising strategies in field control involves the use of atoxic strains of A. flavus in competitive exclusion studies. In this review, we discuss A. flavus as an agricultural and medical threat and summarize recent research advances in genomics, elucidation of parameters of pathogenicity, and control measures.

Description: Structural and functional genomics investigations are making an important impact on the current understanding and application of microbial agents used for plant disease control. Here, we review the case of Trichoderma spp., the most widely applied biocontrol fungi, which have been extensively studied using a variety of research approaches, including genomics, transcriptomics, proteomics, metabolomics, etc. Known for almost a century for their beneficial effects on plants and the soil, these fungi are the subject of investigations that represent a successful case of translational research, in which 'omics-generated novel understanding is directly translated in to new or improved crop treatments and management methods. We present an overview of the latest discoveries on the Trichoderma expressome and metabolome, of the complex and diverse biotic interactions established in nature by these microbes, and of their proven or potential importance to agriculture and industry.

Description: Biocontrol fungi (BCF) are agents that control plant diseases. These include the well-known Trichoderma spp. and the recently described Sebacinales spp. They have the ability to control numerous foliar, root, and fruit pathogens and even invertebrates such as nematodes. However, this is only a subset of their abilities. We now know that they also have the ability to ameliorate a wide range of abiotic stresses, and some of them can also alleviate physiological stresses such as seed aging. They can also enhance nutrient uptake in plants and can substantially increase nitrogen use efficiency in crops. These abilities may be more important to agriculture than disease control. Some strains also have abilities to improve photosynthetic efficiency and probably respiratory activities of plants. All of these capabilities are a consequence of their abilities to reprogram plant gene expression, probably through activation of a limited number of general plant pathways.

Description: Some of the most agriculturally important plant-parasitic nematodes (PPNs) harbor endosymbionts. Extensive work in other systems has shown that endosymbionts can have major effects on host virulence and biology. This review highlights the discovery, development, and diversity of PPN endosymbionts, incorporating inferences from genomic data. Cardinium, reported from five PPN hosts to date, is characterized by its presence in the esophageal glands and other tissues, with a discontinuous distribution across populations, and genomic data suggestive of horizontal gene exchange. Xiphinematobacter occurs in at least 27 species of dagger nematode in the ovaries and gut epithelial cells, where genomic data suggest it may serve in nutritional supplementation. Wolbachia, reported in just three PPNs, appears to have an ancient history in the Pratylenchidae and displays broad tissue distribution and genomic features intermediate between parasitic and reproductive groups. Finally, a model is described that integrates these insights to explain patterns of endosymbiont replacement.

Description: Root border cells separate from plant root tips and disperse into the soil environment. In most species, each root tip can produce thousands of metabolically active cells daily, with specialized patterns of gene expression. Their function has been an enduring mystery. Recent studies suggest that border cells operate in a manner similar to mammalian neutrophils: Both cell types export a complex of extracellular DNA (exDNA) and antimicrobial proteins that neutralize threats by trapping pathogens and thereby preventing invasion of host tissues. Extracellular DNases (exDNases) of pathogens promote virulence and systemic spread of the microbes. In plants, adding DNase I to root tips eliminates border cell extracellular traps and abolishes root tip resistance to infection. Mutation of genes encoding exDNase activity in plant-pathogenic bacteria (Ralstonia solanacearum) and fungi (Cochliobolus heterostrophus) results in reduced virulence. The study of exDNase activities in plant pathogens may yield new targets for disease control.

Description: Strigolactones (SLs) were originally isolated from plant root exudates as germination stimulants for root parasitic plants of the family Orobanchaceae, including witchweeds (Striga spp.), broomrapes (Orobanche and Phelipanche spp.), and Alectra spp., and so were regarded as detrimental to the producing plants. Their role as indispensable chemical signals for root colonization by symbiotic arbuscular mycorrhizal fungi was subsequently unveiled, and SLs then became recognized as beneficial plant metabolites. In addition to these functions in the rhizosphere, it has been recently shown that SLs or their metabolites are a novel class of plant hormones that inhibit shoot branching. Furthermore, SLs are suggested to have other biological functions in rhizosphere communications and in plant growth and development.

Description: Land plants interact with microbes primarily at roots. Despite the importance of root microbial communities for health and nutrient uptake, the current understanding of the complex plant-microbe interactions in the rhizosphere is still in its infancy. Roots provide different microhabitats at the soil-root interface: rhizosphere soil, rhizoplane, and endorhizosphere. We discuss technical aspects of their differentiation that are relevant for the functional analysis of their different microbiomes, and we assess PCR (polymerase chain reaction)-based methods to analyze plant-associated bacterial communities. Development of novel primers will allow a less biased and more quantitative view of these global hotspots of microbial activity. Based on comparison of microbiome data for the different root-soil compartments and on knowledge of bacterial functions, a three-step enrichment model for shifts in community structure from bulk soil toward roots is presented. To unravel how plants shape their microbiome, a major research field is likely to be the coupling of reductionist and molecular ecological approaches, particularly for specific plant genotypes and mutants, to clarify causal relationships in complex root communities.

Description: Nonhost resistance is a broad-spectrum plant defense that provides immunity to all members of a plant species against all isolates of a microorganism that is pathogenic to other plant species. Upon landing on the surface of a nonhost plant species, a potential bacterial pathogen initially encounters preformed and, later, induced plant defenses. One of the initial defense responses from the plant is pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI). Nonhost plants also have mechanisms to detect nonhost-pathogen effectors and can trigger a defense response referred to as effector-triggered immunity (ETI). This nonhost resistance response often results in a hypersensitive response (HR) at the infection site. This review provides an overview of these plant defense strategies. We enumerate plant genes that impart nonhost resistance and the bacterial counter-defense strategies. In addition, prospects for application of nonhost resistance to achieve broad-spectrum and durable resistance in crop plants are also discussed.

Description: Many fungi can live both saprophytically and as endophyte or pathogen inside a living plant. In both environments, complex organic polymers are used as sources of nutrients. Propagation inside a living host also requires the ability to respond to immune responses of the host. We review current knowledge of how plant-pathogenic fungi do this. First, we look at how fungi change their global gene expression upon recognition of the host environment, leading to secretion of effectors, enzymes, and secondary metabolites; changes in metabolism; and defense against toxic compounds. Second, we look at what is known about the various cues that enable fungi to sense the presence of living plant cells. Finally, we review literature on transcription factors that participate in gene expression in planta or are suspected to be involved in that process because they are required for the ability to cause disease.

Description: Many high-risk plant pathogens are transported over long distances (hundreds of meters to thousands of kilometers) in the atmosphere. The ability to track the movement of these pathogens in the atmosphere is essential for forecasting disease spread and establishing effective quarantine measures. Here, we discuss the scales of atmospheric dispersal of plant pathogens along a transport continuum (pathogen scale, farm scale, regional scale, and continental scale). Growers can use risk information at each of these dispersal scales to assist in making plant disease management decisions, such as the timely application of appropriate pesticides. Regional- and continental-scale atmospheric features known as Lagrangian coherent structures (LCSs) may shuffle plant pathogens along highways in the sky. A promising new method relying on overlapping turbulent back-trajectories of pathogen-laden parcels of air may assist in localizing potential inoculum sources, informing local and/or regional management efforts such as conservation tillage. The emergence of unmanned aircraft systems (UASs, or drones) to sample plant pathogens in the lower atmosphere, coupled with source localization efforts, could aid in mitigating the spread of high-risk plant pathogens.

Description: The devastating wheat blast disease first emerged in Brazil in 1985. The disease was restricted to South America until 2016, when a series of grain imports from Brazil led to a wheat blast outbreak in Bangladesh. Wheat blast is caused by Pyricularia graminis-tritici ( Pygt), a species genetically distinct from the Pyricularia oryzae species that causes rice blast. Pygt has high genetic and phenotypic diversity and a broad host range that enables it to move back and forth between wheat and other grass hosts. Recombination is thought to occur mainly on the other grass hosts, giving rise to the highly diverse Pygt population observed in wheat fields. This review brings together past and current knowledge about the history, etiology, epidemiology, physiology, and genetics of wheat blast and discusses the future need for integrated management strategies. The most urgent current need is to strengthen quarantine and biosafety regulations to avoid additional spread of the pathogen to disease-free countries. International breeding efforts will be needed to develop wheat varieties with more durable resistance.

Description: Boxwood blight, caused by Calonectria pseudonaviculata and Calonectria henricotiae, has had devastating effects in gardens since its first appearance in the United Kingdom in 1994. The disease affects two other plants in the Buxaceae: sweet box ( Sarcococca spp.) and pachysandra ( Pachysandra spp.). C. pseudonaviculata was likely introduced to Europe by nursery trade from East Asia on an ornamental species and then to western Asia and North America. Thus far, C. henricotiae has been seen only in Europe. Boxwood, valued at $126 million wholesale per year in the United States alone, is now besieged by an aggressive foliar blight active over a broad temperature range when there are long periods of leaf wetness. Research on inoculum, means of dissemination, cultivar susceptibility, environmental influences, fungicides, sanitizers, and detection methods has vastly improved knowledge of this new invasive disease in a short time. Boxwood with genetic resistance to the disease is critically needed.

Description: Pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs) are detected as nonself by host pattern recognition receptors (PRRs) and activate pattern-triggered immunity (PTI). Microbial invasions often trigger the production of host-derived endogenous signals referred to as danger- or damage-associated molecular patterns (DAMPs), which are also perceived by PRRs to modulate PTI responses. Collectively, PTI contributes to host defense against infections by a broad range of pathogens. Remarkable progress has been made toward demonstrating the cellular and physiological responses upon pattern recognition, elucidating the molecular, biochemical, and genetic mechanisms of PRR activation, and dissecting the complex signaling networks that orchestrate PTI responses. In this review, we present an update on the current understanding of how plants recognize and respond to nonself patterns, a process from which the seemingly chaotic responses form into a harmonic defense.

Description: Organic amendments (OAs) and soilborne biocontrol agents or beneficial microbes (BMs) have been extensively studied and applied worldwide in most agriculturally important plant species. However, poor integration of research and technical approaches has limited the development of effective disease management practices based on the combination of these two bio-based strategies. Insights into the importance of the plant-associated microbiome for crop productivity, which can be modified or modulated by introducing OAs and/or BMs, are providing novel opportunities to achieve the goal of long-term disease control. This review discusses novel ways of functionally characterizing OAs and how they may be used to promote the effect of added biocontrol agents and/or beneficial soil microbiota to support natural suppressiveness of plant pathogens.

Description: Plants inhabit environments crowded with infectious microbes that pose constant threats to their survival. Necrotrophic pathogens are notorious for their aggressive and wide-ranging virulence strategies that promote host cell death and acquire nutrients for growth and reproduction from dead cells. This lifestyle constitutes the axis of their pathogenesis and virulence strategies and marks contrasting immune responses to biotrophic pathogens. The diversity of virulence strategies in necrotrophic species corresponds to multifaceted host immune response mechanisms. When effective, the plant immune system disarms the infectious necrotroph of its pathogenic arsenal or attenuates its effect, restricting further ingress and disease symptom development. Simply inherited resistance traits confer protection against host-specific necrotrophs (HSNs), whereas resistance to broad host-range necrotrophs (BHNs) is complex. Components of host genetic networks, as well as the molecular and cellular processes that mediate host immune responses to necrotrophs, are being identified. In this review, recent advances in our understanding of plant immune responses to necrotrophs and comparison with responses to biotrophic pathogens are summarized, highlighting common and contrasting mechanisms.

Description: With the advent of recombinant DNA techniques, the field of molecular plant pathology witnessed dramatic shifts in the 1970s and 1980s. The new and conventional methodologies of bacterial molecular genetics put bacteria center stage. The discovery in the mid-1980s of the hrp/hrc gene cluster and the subsequent demonstration that it encodes a type III secretion system (T3SS) common to Gram negative bacterial phytopathogens, animal pathogens, and plant symbionts was a landmark in molecular plant pathology. Today, T3SS has earned a central role in our understanding of many fundamental aspects of bacterium-plant interactions and has contributed the important concept of interkingdom transfer of effector proteins determining race-cultivar specificity in plant-bacterium pathosystems. Recent developments in genomics, proteomics, and structural biology enable detailed and comprehensive insights into the functional architecture, evolutionary origin, and distribution of T3SS among bacterial pathogens and support current research efforts to discover novel antivirulence drugs.

Description: Trichoderma species are widely used in agriculture and industry as biopesticides and sources of enzymes, respectively. These fungi reproduce asexually by production of conidia and chlamydospores and in wild habitats by ascospores. Trichoderma species are efficient mycoparasites and prolific producers of secondary metabolites, some of which have clinical importance. However, the ecological or biological significance of this metabolite diversity is sorely lagging behind the chemical significance. Many strains produce elicitors and induce resistance in plants through colonization of roots. Seven species have now been sequenced. Comparison of a primarily saprophytic species with two mycoparasitic species has provided striking contrasts and has established that mycoparasitism is an ancestral trait of this genus. Among the interesting outcomes of genome comparison is the discovery of a vast repertoire of secondary metabolism pathways and of numerous small cysteine-rich secreted proteins. Genomics has also facilitated investigation of sexual crossing in Trichoderma reesei, suggesting the possibility of strain improvement through hybridization.

Description: Xanthomonads are bacterial plant pathogens that cause diseases on many plant species, including important crops. Key to pathogenicity of most Xanthomonas pathovars is a Hrp-type III secretion (T3S) system that translocates effector proteins into plant cells. Within the eukaryotic cell, the effectors are thought to perform a variety of tasks to support bacterial virulence, proliferation, and dissemination. We are only beginning to understand the host targets of different effectors. The largest effector family found in Xanthomonas spp. is the AvrBs3/PthA or TAL (transcription activator-like) family. TAL effectors act as transcriptional activators in the plant cell nucleus. Specificity of TAL effectors is determined by a novel modular DNA-binding domain. Here, we describe the discovery of TAL effectors and their structure, activity, and host targets.

Description: Bacterial soft rot is a disease complex caused by multiple genera of gram-negative and gram-positive bacteria, with Dickeya and Pectobacterium being the most widely studied soft-rot bacterial pathogens. In addition to soft rot, these bacteria also cause blackleg of potato, foot rot of rice, and bleeding canker of pear. Multiple Dickeya and Pectobacterium species cause the same symptoms on potato, complicating epidemiology and disease resistance studies. The primary pathogen species present in potato-growing regions differs over time and space, further complicating disease management. Genomics technologies are providing new management possibilities, including improved detection and biocontrol methods that may finally allow effective disease management. The recent development of inbred diploid potato lines is also having a major impact on studying soft-rot pathogens because it is now possible to study soft-rot disease in model plant species that produce starchy vegetative storage organs. Together, these new discoveries have changed how we face diseases caused by these pathogens.