In the US Corn Belt, a recent doubling in commodity prices has created incentives for landowners to convert grassland to corn and soybean cropping. Here, we use land cover data from the National ...Agricultural Statistics Service Cropland Data Layer to assess grassland conversion from 2006 to 2011 in the Western Corn Belt (WCB): five states including North Dakota, South Dakota, Nebraska, Minnesota, and Iowa. Our analysis identifies areas with elevated rates of grass-to-corn/soy conversion (1.0–5.4% annually). Across the WCB, we found a net decline in grass-dominated land cover totaling nearly 530,000 ha. With respect to agronomic attributes of lands undergoing grassland conversion, corn/soy production is expanding onto marginal lands characterized by high erosion risk and vulnerability to drought. Grassland conversion is also concentrated in close proximity to wetlands, posing a threat to waterfowl breeding in the Prairie Pothole Region. Longer-term land cover trends from North Dakota and Iowa indicate that recent grassland conversion represents a persistent shift in land use rather than short-term variability in crop rotation patterns. Our results show that the WCB is rapidly moving down a pathway of increased corn and soybean cultivation. As a result, the window of opportunity for realizing the benefits of a biofuel industry based on perennial bioenergy crops, rather than corn ethanol and soy biodiesel, may be closing in the WCB.
Tumors are largely classified by histologic appearance, yet morphologic features do not necessarily predict cellular origin. To determine the origin of pancreatic ductal adenocarcinoma (PDA), we ...labeled and traced pancreatic cell populations after induction of a PDA-initiating Kras mutation. Our studies reveal that ductal and stem-like centroacinar cells are surprisingly refractory to oncogenic transformation, whereas acinar cells readily form PDA precursor lesions with ductal features. We show that formation of acinar-derived premalignant lesions depends on ectopic induction of the ductal gene Sox9. Moreover, when concomitantly expressed with oncogenic Kras, Sox9 accelerates formation of premalignant lesions. These results provide insight into the cellular origin of PDA and suggest that its precursors arise via induction of a duct-like state in acinar cells.
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► Preneoplastic lesions rarely arise from pancreatic ductal/centroacinar cells ► Acinar cells are the predominant cells of origin for pancreatic preneoplastic lesions ► Initiation of pancreatic cancer depends on acinar induction of the ductal gene Sox9 ► Sox9 synergizes with KrasG12D and injury in acinar-to-ductal cell reprogramming
Reprogramming of pancreatic exocrine cells into cells resembling beta cells may provide a strategy for treating diabetes. Here we show that transient administration of epidermal growth factor and ...ciliary neurotrophic factor to adult mice with chronic hyperglycemia efficiently stimulates the conversion of terminally differentiated acinar cells to beta-like cells. Newly generated beta-like cells are epigenetically reprogrammed, functional and glucose responsive, and they reinstate normal glycemic control for up to 248 d. The regenerative process depends on Stat3 signaling and requires a threshold number of Neurogenin 3 (Ngn3)-expressing acinar cells. In contrast to previous work demonstrating in vivo conversion of acinar cells to beta-like cells by viral delivery of exogenous transcription factors, our approach achieves acinar-to-beta-cell reprogramming through transient cytokine exposure rather than genetic modification.
The prospective white matter (PWM) in the nascent cerebellum contains a transient germinal compartment that produces all postnatally born GABAergic inhibitory interneurons and astrocytes. However, ...little is known about the molecular identity and developmental potential of resident progenitors or key regulatory niche signals. Here, we show that neural stem-cell-like primary progenitors (TncYFP-low CD133+) generate intermediate astrocyte (TncYFP-low CD15+) precursors and GABAergic transient amplifying (Ptf1a+) cells. Interestingly, these lineally related but functionally divergent progenitors commonly respond to Sonic hedgehog (Shh), and blockade of reception in TNCYFP-low cells attenuates proliferation in the PWM, reducing both intermediate progenitor classes. Furthermore, we show that Shh produced from distant Purkinje neurons maintains the PWM niche independently of its classical role in regulating granule cell precursor proliferation. Our results indicate that Purkinje neurons maintain a bidirectional signaling axis, driving the production of spatially and functionally opposed inhibitory and excitatory interneurons important for motor learning and cognition.
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•Purkinje neurons signal bidirectionally to expand functionally divergent cell types•Nascent white matter harbors molecularly distinct but lineally related astroglia•Shh signaling maintains the neurogenic niche in nascent white matter•Ptf1a expression marks transiently amplifying GABAergic progenitor pools
Assembly of neurocircuitry requires coordinated generation of excitatory and inhibitory interneurons. Fleming et al. find that Purkinje neurons use Shh to signal bidirectionally, generating excitatory and inhibitory interneurons at distinct locations within the nascent cerebellum. Purkinje-derived Shh also promotes astrocytic white-matter development and thus the niche for inhibitory interneurons.
The male bias in autism spectrum disorder incidence is among the most extreme of all neuropsychiatric disorders, yet the origins of the sex difference remain obscure. Developmentally, males are ...exposed to high levels of testosterone and its byproduct, estradiol. Together these steroids modify the course of brain development by altering neurogenesis, cell death, migration, differentiation, dendritic and axonal growth, synaptogenesis, and synaptic pruning, all of which can be deleteriously impacted during the course of developmental neuropsychiatric disorders. Elucidating the cellular mechanisms by which steroids modulate brain development provides valuable insights into how these processes may go awry. An emerging theme is the role of inflammatory signaling molecules and the innate immune system in directing brain masculinization, the evidence for which we review here. Evidence is also emerging that the neuroimmune system is overactivated in individuals with autism spectrum disorder. These combined observations lead us to propose that the natural process of brain masculinization puts males at risk by moving them closer to a vulnerability threshold that could more easily be breached by inflammation during critical periods of brain development. Two brain regions are highlighted: the preoptic area and the cerebellum. Both are developmentally regulated by the inflammatory prostaglandin E2, but in different ways. Microglia, innate immune cells of the brain, and astrocytes are also critical contributors to masculinization and illustrate the importance of nonneuronal cells to the health of the developing brain.
Agile Project Management, Assurance and Auditing - A practical
guide for auditors, reviewers and project teams
Adopting the Agile methodology helps organisations develop the
flexibility and ...adaptability necessary in such fast-paced
environments. The use of Agile for non-IT projects - such as
introducing new products, refurbishing retail outlets, and even
planning and running audits - means that general auditors and other
reviewers, as well as IT specialist auditors, need to understand
Agile practices.
This guide provides an overview of Agile for auditors, reviewers
and project teams
This guide covers:
Agile project management audit objectives;
The risks covered by each objective;
What controls to expect and how these can be audited;
Case studies illustrating Agile project initiation and
high-level requirements; and
Hints and tips for performing an audit review.
For experienced auditors and project management teams, this
guide demonstrates how they can adapt and reuse audit skills that
they may have gained during traditional waterfall, CRAMM (CCTA Risk
Analysis and Management Method), or PRINCE2® implementation/audits.
For those less experienced, it will encourage them to consider
these good practices and their application to Agile audits.
An ideal introduction to Agile project management for auditors,
project managers, Agile teams and students
In the mammalian pancreas, endocrine cells undergo lineage allocation upon emergence from a bipotent duct/endocrine progenitor pool, which resides in the "trunk epithelium." Major questions remain ...regarding how niche environments are organized within this epithelium to coordinate endocrine differentiation with programs of epithelial growth, maturation, and morphogenesis. We used EdU pulse-chase and tissue-reconstruction approaches to analyze how endocrine progenitors and their differentiating progeny are assembled within the trunk as it undergoes remodeling from an irregular plexus of tubules to form the eventual mature, branched ductal arbor. The bulk of endocrine progenitors is maintained in an epithelial "plexus state," which is a transient intermediate during epithelial maturation within which endocrine cell differentiation is continually robust and surprisingly long-lived. Within the plexus, local feedback effects derived from the differentiating and delaminating endocrine cells nonautonomously regulate the flux of endocrine cell birth as well as proliferative growth of the bipotent cell population using Notch-dependent and Notch-independent influences, respectively. These feedback effects in turn maintain the plexus state to ensure prolonged allocation of endocrine cells late into gestation. These findings begin to define a niche-like environment guiding the genesis of the endocrine pancreas and advance current models for how differentiation is coordinated with the growth and morphogenesis of the developing pancreatic epithelium.
Abstract Truancy has been a persistent problem in the United States for more than 100 years. Although truancy is commonly reported as a risk factor for substance use, delinquency, dropout, and a host ...of other negative outcomes for youth, there has been surprisingly little empirical investigation into understanding the causes and correlates of truancy using large, nationally representative samples. Using the adolescent sample ( N = 17,482) of the 2009 National Survey on Drug Use and Health (NSDUH), this study presents the prevalence of truancy and examines individual, school engagement, parental, and behavioral correlates of truancy. Overall, 11% of adolescents between the ages of 12–17 reported skipping school in the past 30 days. Results from multinomial logistic regression models indicate skipping school was robustly associated with an increased probability of reporting externalizing behaviors, less parental involvement, and engagement and lower grades in school. Implications for theory, prevention, and policy are discussed.
Asymmetric development of the vertebrate embryo has fascinated embryologists for over a century. Much has been learned since the asymmetric Nodal signaling cascade in the left lateral plate mesoderm ...was detected, and began to be unraveled over the past decade or two. When and how symmetry is initially broken, however, has remained a matter of debate. Two essentially mutually exclusive models prevail. Cilia-driven leftward flow of extracellular fluids occurs in mammalian, fish and amphibian embryos. A great deal of experimental evidence indicates that this flow is indeed required for symmetry breaking. An alternative model has argued, however, that flow simply acts as an amplification step for early asymmetric cues generated by ion flux during the first cleavage divisions. In this review we critically evaluate the experimental basis of both models. Although a number of open questions persist, the available evidence is best compatible with flow-based symmetry breakage as the archetypical mode of symmetry breakage.
•Serotonin does not redistribute in cleavage stage frog embryos.•Spemann׳s organizer is instrumental for the left–right organizer.•Experimental and genetic data are incompatible with the ion flux model.•Genetic data cement the role of cilia in vertebrate left–right axis formation.•Cilia-driven leftward flow is causative for symmetry breakage in Xenopus.
Pancreas development begins with the formation of buds at specific sites in the embryonic foregut endoderm. We used recombination-based lineage tracing in vivo to show that Ptf1a (also known as ...PTF1-p48) is expressed at these early stages in the progenitors of pancreatic ducts, exocrine and endocrine cells, rather than being an exocrine-specific gene as previously described. Moreover, inactivation of Ptf1a switches the character of pancreatic progenitors such that their progeny proliferate in and adopt the normal fates of duodenal epithelium, including its stem-cell compartment. Consistent with the proposal that Ptf1a supports the specification of precursors of all three pancreatic cell types, transgene-based expression of Pdx1, a gene essential to pancreas formation, from Ptf1a cis-regulatory sequences restores pancreas tissue to Pdx1-null mice that otherwise lack mature exocrine and endocrine cells because of an early arrest in organogenesis. These experiments provide evidence that Ptf1a expression is specifically connected to the acquisition of pancreatic fate by undifferentiated foregut endoderm.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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