A cyclic (alkyl)(amino)carbene (CAAC) was found to undergo unprecedented rearrangements and transformations of its core structure in the presence of Group 1 and 2 metals. Although the carbene was ...also found to be prone to intramolecular C−H activation, it was competent for intermolecular activation of a variety of sp‐, sp2‐, and sp3‐hybridized C−H bonds. Double C−F activation of hexafluorobenzene was also observed in this work. These processes all hold relevance to the role of these carbenes in catalysis, as well as to their use in the synthesis of new and unusual main group or transition metal complexes.
Non‐innocent CAACs: A cyclic (alkyl)(amino)carbene (CAAC) was found to undergo unprecedented rearrangements and transformations of its core structure in the presence of Group 1 and 2 metals. Examples of C−H and C−F activation utilizing the carbene are also reported.
Mucosal surfaces are lined by epithelial cells. In the intestine, the epithelium establishes a selectively permeable barrier that supports nutrient absorption and waste secretion while preventing ...intrusion by luminal materials. Intestinal epithelia therefore play a central role in regulating interactions between the mucosal immune system and luminal contents, which include dietary antigens, a diverse intestinal microbiome, and pathogens. The paracellular space is sealed by the tight junction, which is maintained by a complex network of protein interactions. Tight junction dysfunction has been linked to a variety of local and systemic diseases. Two molecularly and biophysically distinct pathways across the intestinal tight junction are selectively and differentially regulated by inflammatory stimuli. This review discusses the mechanisms underlying these events, their impact on disease, and the potential of using these as paradigms for development of tight junction-targeted therapeutic interventions.
The primary structural component of the bacterial cell wall is peptidoglycan, which is essential for viability and the synthesis of which is the target for crucial antibiotics
. Peptidoglycan is a ...single macromolecule made of glycan chains crosslinked by peptide side branches that surrounds the cell, acting as a constraint to internal turgor
. In Gram-positive bacteria, peptidoglycan is tens of nanometres thick, generally portrayed as a homogeneous structure that provides mechanical strength
. Here we applied atomic force microscopy
to interrogate the morphologically distinct Staphylococcus aureus and Bacillus subtilis species, using live cells and purified peptidoglycan. The mature surface of live cells is characterized by a landscape of large (up to 60 nm in diameter), deep (up to 23 nm) pores constituting a disordered gel of peptidoglycan. The inner peptidoglycan surface, consisting of more nascent material, is much denser, with glycan strand spacing typically less than 7 nm. The inner surface architecture is location dependent; the cylinder of B. subtilis has dense circumferential orientation, while in S. aureus and division septa for both species, peptidoglycan is dense but randomly oriented. Revealing the molecular architecture of the cell envelope frames our understanding of its mechanical properties and role as the environmental interface
, providing information complementary to traditional structural biology approaches.
A fundamental function of the intestinal epithelium is to act as a barrier that limits interactions between luminal contents such as the intestinal microbiota, the underlying immune system and the ...remainder of the body, while supporting vectorial transport of nutrients, water and waste products. Epithelial barrier function requires a contiguous layer of cells as well as the junctions that seal the paracellular space between epithelial cells. Compromised intestinal barrier function has been associated with a number of disease states, both intestinal and systemic. Unfortunately, most current clinical data are correlative, making it difficult to separate cause from effect in interpreting the importance of barrier loss. Some data from experimental animal models suggest that compromised epithelial integrity might have a pathogenic role in specific gastrointestinal diseases, but no FDA-approved agents that target the epithelial barrier are presently available. To develop such therapies, a deeper understanding of both disease pathogenesis and mechanisms of barrier regulation must be reached. Here, we review and discuss mechanisms of intestinal barrier loss and the role of intestinal epithelial barrier function in pathogenesis of both intestinal and systemic diseases. We conclude with a discussion of potential strategies to restore the epithelial barrier.
A family of group 15 MIII pyridine dipyrrolide complexes has been prepared and fully characterized; the reduction of these complexes was investigated with traditional strong metal reductants, which ...led either to over-reduction in the case of Mg and Zn or to ligand redistribution and “ate” complex formation when KC8 was used. However, by utilizing organosilanes as soluble reductants, the ring opening and two electron reduction of thf solvent was observed with concomitant formation of Bi–C and Si–O bonds; this is an example of a main group complex that is capable of ring opening a cyclic ether in the absence of additional metal reducing agents. The proposed BiII intermediate in this mechanism could be trapped using the stable organic radical TEMPO.
We determined the number of permits for oil and gas activities in 14 coastal Louisiana parishes from 1900 to 2017, compared them to land loss on this coast, and estimated their restoration potential. ...A total of 76,247 oil and gas recovery wells were permitted, of which 35,163 (46%) were on land (as of 2010) and 27,483 of which are officially abandoned. There is a direct spatial and temporal relationship between the number of these permits and land loss, attributable to the above and belowground changes in hydrology resulting from the dredged material levees placed parallel to the canal (spoil banks). These hydrologic modifications cause various direct and indirect compromises to plants and soils resulting in wetland collapse. Although oil and gas recovery beneath southern Louisiana wetlands has dramatically declined since its peak in the early 1960s, it has left behind spoil banks with a total length sufficient to cross coastal Louisiana 79 times from east to west. Dragging down the remaining material in the spoil bank back into the canal is a successful restoration technique that is rarely applied in Louisiana, but could be a dramatically cost-effective and proven long-term strategy if political will prevails. The absence of a State or Federal backfilling program is a huge missed opportunity to: 1) conduct cost-effective restoration at a relatively low cost, and, 2) conduct systematic restoration monitoring and hypothesis testing that advances knowledge and improves the efficacy of future attempts. The price of backfilling all canals is about $335 million dollars, or 0.67% of the State's Master Plan for restoration and a pittance of the economic value gained from extracting the oil and gas beneath over the last 100 years.
Flow diverters are increasingly used in the endovascular treatment of intracranial aneurysms. Our aim was to determine neurologic complication rates following Pipeline Embolization Device placement ...for intracranial aneurysm treatment in a real-world setting.
We retrospectively evaluated all patients with intracranial aneurysms treated with the Pipeline Embolization Device between July 2008 and February 2013 in 17 centers worldwide. We defined 4 subgroups: internal carotid artery aneurysms of ≥10 mm, ICA aneurysms of <10 mm, other anterior circulation aneurysms, and posterior circulation aneurysms. Neurologic complications included spontaneous rupture, intracranial hemorrhage, ischemic stroke, permanent cranial neuropathy, and mortality. Comparisons were made with t tests or ANOVAs for continuous variables and the Pearson χ(2) or Fisher exact test for categoric variables.
In total, 793 patients with 906 aneurysms were included. The neurologic morbidity and mortality rate was 8.4% (67/793), highest in the posterior circulation group (16.4%, 9/55) and lowest in the ICA <10-mm group (4.8%, 14/294) (P = .01). The spontaneous rupture rate was 0.6% (5/793). The intracranial hemorrhage rate was 2.4% (19/793). Ischemic stroke rates were 4.7% (37/793), highest in patients with posterior circulation aneurysms (7.3%, 4/55) and lowest in the ICA <10-mm group (2.7%, 8/294) (P = .16). Neurologic mortality was 3.8% (30/793), highest in the posterior circulation group (10.9%, 6/55) and lowest in the anterior circulation ICA <10-mm group (1.4%, 4/294) (P < .01).
Aneurysm treatment with the Pipeline Embolization Device is associated with the lowest complication rates when used to treat small ICA aneurysms. Procedure-related morbidity and mortality are higher in the treatment of posterior circulation and giant aneurysms.
Resveratrol for Alzheimer's disease Sawda, Christine; Moussa, Charbel; Turner, R. Scott
Annals of the New York Academy of Sciences,
September 2017, Letnik:
1403, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The amyloid hypothesis suggests that the progressive accumulation and deposition of central nervous system (CNS) amyloid with aging is the proximate cause of Alzheimer's disease (AD). Thus, targeting ...molecular mechanisms of aging may be a viable treatment approach. Caloric restriction prevents diseases of aging, including AD, in animal models, perhaps by activation of sirtuins. The sirtuins (e.g., mammalian SIRT1) are deacetylases that link energy balance (NAD+/NADH) to regulation of gene transcription. Resveratrol is a potent activator of SIRT1, and thus may mimic caloric restriction to prevent diseases of aging. We conducted a randomized, double‐blind, placebo‐controlled, phase II trial of resveratrol for individuals with mild‐to‐moderate AD. Resveratrol (1) is detectable in cerebrospinal fluid (at low nanomolar levels), (2) is safe and well tolerated, (3) alters AD biomarker trajectories, (4) preserves blood–brain barrier integrity, and (5) modulates the CNS immune response. Further studies are needed to determine the safety and efficacy of resveratrol and the validity of this approach in the treatment and prevention of AD and other diseases of aging.
The concept of ecosystems services has become an important model for linking the functioning of ecosystems to human welfare. Understanding this link is critical for a wide-range of decision-making ...contexts. While there have been several attempts to come up with a classification scheme for ecosystem services, there has not been an agreed upon, meaningful and consistent definition for ecosystem services. In this paper we offer a definition of ecosystem services that is likely to be operational for ecosystem service research and several classification schemes. We argue that any attempt at classifying ecosystem services should be based on both the characteristics of the ecosystems of interest and a decision context for which the concept of ecosystem services is being mobilized. Because of this there is not one classification scheme that will be adequate for the many contexts in which ecosystem service research may be utilized. We discuss several examples of how classification schemes will be a function of both ecosystem and ecosystem service characteristics and the decision-making context.
There are conflicting predictions of climate change effects and landuse on the discharge of the Mississippi River-the largest river in North America. Are discharges becoming higher or lower, and if ...they did change, then when? To address these uncertainties I compiled a two-hundred-year long dataset of the annual average, minimum, and maximum discharges at five stations draining the Mississippi River watershed: at Clinton, IA, Herman, MO, St. Louis, MO, Louisville, KY, and Vicksburg, MS. A spline/Lowess analysis tested for trends and inflection points. All three discharge metrics increased, and the minimum annual discharge increased faster than either the annual maximum discharge or annual average discharge. A regression analysis of variations in average discharges from 1950 to 2020 at these five locations demonstrates correlations to the air pressure differentials represented in the North Atlantic Oscillation (NAO) Index for January, February and March. The longest data set, for the Mississippi River at Vicksburg, demonstrates a similar direct relationship with the NAO Index from 1826 to 1969. After 1969, however, the relationship between discharge and the NAO Index is insignificant even though the range of Index values overlap for the two intervals. A breakpoint and rise in discharge ca. 1970 is consistent with well-documented land cover and land use changes occurring then that resulted in reduced evapotranspiration as homogenous cropping systems were established, and a higher percent of precipitation was routed into groundwater and baseflow. The Bonnet Carré Spillway at New Orleans, LA, is being opened more frequently to reduce flood threats as the river's stage increasingly reaches the threshold for opening it. Significant water quality impairments in the coastal zone will appear or be sustained with these openings. These data may be useful for climate change assessments through modeling or synthetic assessments in combination with other data sets.
PDF
