Numerous studies have documented increases in matrix metalloproteinases (MMPs), specifically MMP-9 levels following stroke, with such perturbations associated with disruption of the blood brain ...barrier (BBB), increased risk of hemorrhagic complications, and worsened outcome. Despite this, controversy remains as to which cells release MMP-9 at the normal and pathological BBB, with even less clarity in the context of stroke. This may be further complicated by the influence of tissue plasminogen activator (tPA) treatment. The aim of the present review is to examine the relationship between neutrophils, MMP-9 and tPA following ischemic stroke to elucidate which cells are responsible for the increases in MMP-9 and resultant barrier changes and hemorrhage observed following stroke.
This review proposes that lipopolysaccharide (LPS, found in the wall of all Gram-negative bacteria) could play a role in causing sporadic Alzheimer's disease (AD). This is based in part upon recent ...studies showing that: Gram-negative
bacteria can form extracellular amyloid; bacterial-encoded 16S rRNA is present in all human brains with over 70% being Gram-negative bacteria; ultrastructural analyses have shown microbes in erythrocytes of AD patients; blood LPS levels in AD patients are 3-fold the levels in control; LPS combined with focal cerebral ischemia and hypoxia produced amyloid-like plaques and myelin injury in adult rat cortex. Moreover, Gram-negative bacterial LPS was found in aging control and AD brains, though LPS levels were much higher in AD brains. In addition, LPS co-localized with amyloid plaques, peri-vascular amyloid, neurons, and oligodendrocytes in AD brains. Based upon the postulate LPS caused oligodendrocyte injury, degraded Myelin Basic Protein (dMBP) levels were found to be much higher in AD compared to control brains. Immunofluorescence showed that the dMBP co-localized with β amyloid (Aβ) and LPS in amyloid plaques in AD brain, and dMBP and other myelin molecules were found in the walls of vesicles in periventricular White Matter (WM). These data led to the hypothesis that LPS acts on leukocyte and microglial TLR4-CD14/TLR2 receptors to produce NFkB mediated increases of cytokines which increase Aβ levels, damage oligodendrocytes and produce myelin injury found in AD brain. Since Aβ
is also an agonist for TLR4 receptors, this could produce a vicious cycle that accounts for the relentless progression of AD. Thus, LPS, the TLR4 receptor complex, and Gram-negative bacteria might be treatment or prevention targets for sporadic AD.
We determine the low-redshift field galaxy stellar mass function (GSMF) using an area of 143 deg2 from the first three years of the Galaxy And Mass Assembly (GAMA) survey. The magnitude limits of ...this redshift survey are r < 19.4 mag over two-thirds and 19.8 mag over one-third of the area. The GSMF is determined from a sample of 5210 galaxies using a density-corrected maximum volume method. This efficiently overcomes the issue of fluctuations in the number density versus redshift. With H
0= 70 km s−1 Mpc−1, the GSMF is well described between 108 and 1011.5 M⊙ using a double Schechter function with
,
, α1=−0.35,
and α2=−1.47. This result is more robust to uncertainties in the flow-model corrected redshifts than from the shallower Sloan Digital Sky Survey main sample (r < 17.8 mag). The upturn in the GSMF is also seen directly in the i-band and K-band galaxy luminosity functions. Accurately measuring the GSMF below 108 M⊙ is possible within the GAMA survey volume but as expected requires deeper imaging data to address the contribution from low surface-brightness galaxies.
Central nervous system (CNS) injuries, such as stroke, traumatic brain injury (TBI) and spinal cord injury (SCI), are important causes of death and long-term disability worldwide. MicroRNA (miRNA), ...small non-coding RNA molecules that negatively regulate gene expression, can serve as diagnostic biomarkers and are emerging as novel therapeutic targets for CNS injuries. MiRNA-based therapeutics include miRNA mimics and inhibitors (antagomiRs) to respectively decrease and increase the expression of target genes. In this review, we summarize current miRNA-based therapeutic applications in stroke, TBI and SCI. Administration methods, time windows and dosage for effective delivery of miRNA-based drugs into CNS are discussed. The underlying mechanisms of miRNA-based therapeutics are reviewed including oxidative stress, inflammation, apoptosis, blood–brain barrier protection, angiogenesis and neurogenesis. Pharmacological agents that protect against CNS injuries by targeting specific miRNAs are presented along with the challenges and therapeutic potential of miRNA-based therapies.
Neutrophils have key roles in ischemic brain injury, thrombosis, and atherosclerosis. As such, neutrophils are of great interest as targets to treat and prevent ischemic stroke. After stroke, ...neutrophils respond rapidly promoting blood–brain barrier disruption, cerebral edema, and brain injury. A surge of neutrophil-derived reactive oxygen species, proteases, and cytokines are released as neutrophils interact with cerebral endothelium. Neutrophils also are linked to the major processes that cause ischemic stroke, thrombosis, and atherosclerosis. Thrombosis is promoted through interactions with platelets, clotting factors, and release of prothrombotic molecules. In atherosclerosis, neutrophils promote plaque formation and rupture by generating oxidized-low density lipoprotein, enhancing monocyte infiltration, and degrading the fibrous cap. In experimental studies targeting neutrophils can improve stroke. However, early human studies have been met with challenges, and suggest that selective targeting of neutrophils may be required. Several properties of neutrophil are beneficial and thus may important to preserve in patients with stroke including antimicrobial, antiinflammatory, and neuroprotective functions.
Galaxy And Mass Assembly (GAMA): stellar mass estimates Taylor, Edward N.; Hopkins, Andrew M.; Baldry, Ivan K. ...
Monthly notices of the Royal Astronomical Society,
December 2011, Letnik:
418, Številka:
3
Journal Article
Recenzirano
Odprti dostop
This paper describes the first catalogue of photometrically derived stellar mass estimates for intermediate-redshift (z < 0.65; median z= 0.2) galaxies in the Galaxy And Mass Assembly (GAMA) ...spectroscopic redshift survey. These masses, as well as the full set of ancillary stellar population parameters, will be made public as part of GAMA data release 2. Although the GAMA database does include near-infrared (NIR) photometry, we show that the quality of our stellar population synthesis fits is significantly poorer when these NIR data are included. Further, for a large fraction of galaxies, the stellar population parameters inferred from the optical-plus-NIR photometry are formally inconsistent with those inferred from the optical data alone. This may indicate problems in our stellar population library, or NIR data issues, or both; these issues will be addressed for future versions of the catalogue. For now, we have chosen to base our stellar mass estimates on optical photometry only. In light of our decision to ignore the available NIR data, we examine how well stellar mass can be constrained based on optical data alone. We use generic properties of stellar population synthesis models to demonstrate that restframe colour alone is in principle a very good estimator of stellar mass-to-light ratio, M
*/Li
. Further, we use the observed relation between restframe (g−i) and M
*/Li
for real GAMA galaxies to argue that, modulo uncertainties in the stellar evolution models themselves, (g−i) colour can in practice be used to estimate M
*/Li
to an accuracy of ≲0.1 dex (1σ). This 'empirically calibrated' (g−i)-M
*/Li
relation offers a simple and transparent means for estimating galaxies' stellar masses based on minimal data, and so provides a solid basis for other surveys to compare their results to z≲0.4 measurements from GAMA.
Hemorrhagic transformation (HT) is a common complication of ischemic stroke that is exacerbated by thrombolytic therapy. Methods to better prevent, predict, and treat HT are needed. In this review, ...we summarize studies of HT in both animals and humans. We propose that early HT (<18 to 24 hours after stroke onset) relates to leukocyte-derived matrix metalloproteinase-9 (MMP-9) and brain-derived MMP-2 that damage the neurovascular unit and promote blood–brain barrier (BBB) disruption. This contrasts to delayed HT (>18 to 24 hours after stroke) that relates to ischemia activation of brain proteases (MMP-2, MMP-3, MMP-9, and endogenous tissue plasminogen activator), neuroinflammation, and factors that promote vascular remodeling (vascular endothelial growth factor and high-moblity-group-box-1). Processes that mediate BBB repair and reduce HT risk are discussed, including transforming growth factor beta signaling in monocytes, Src kinase signaling, MMP inhibitors, and inhibitors of reactive oxygen species. Finally, clinical features associated with HT in patients with stroke are reviewed, including approaches to predict HT by clinical factors, brain imaging, and blood biomarkers. Though remarkable advances in our understanding of HT have been made, additional efforts are needed to translate these discoveries to the clinic and reduce the impact of HT on patients with ischemic stroke.
Glyphosate, the most widely used herbicide, is linked with environmental harm and there is a drive to replace it in agricultural systems. We model the impacts of discontinuing glyphosate use and ...replacing it with cultural control methods. We simulate winter wheat arable systems reliant on glyphosate and typical in northwest Europe. Removing glyphosate was projected to increase weed abundance, herbicide risk to the environment, and arable plant diversity and decrease food production. Weed communities with evolved resistance to non-glyphosate herbicides were not projected to be disproportionately affected by removing glyphosate, despite the lack of alternative herbicidal control options. Crop rotations with more spring cereals or grass leys for weed control increased arable plant diversity. Stale seedbed techniques such as delayed drilling and choosing ploughing instead of minimum tillage had varying effects on weed abundance, food production, and profitability. Ploughing was the most effective alternative to glyphosate for long-term weed control while maintaining production and profit. Our findings emphasize the need for careful consideration of trade-offs arising in scenarios where glyphosate is removed. Integrated Weed Management (IWM) with more use of cultural control methods offers the potential to reduce chemical use but is sensitive to seasonal variability and can incur negative environmental and economic impacts.
Abstract
While there is significant enthusiasm in the medical community about the use of artificial intelligence (AI) technologies in healthcare, few research studies have sought to assess patient ...perspectives on these technologies. We conducted 15 focus groups examining patient views of diverse applications of AI in healthcare. Our results indicate that patients have multiple concerns, including concerns related to the safety of AI, threats to patient choice, potential increases in healthcare costs, data-source bias, and data security. We also found that patient acceptance of AI is contingent on mitigating these possible harms. Our results highlight an array of patient concerns that may limit enthusiasm for applications of AI in healthcare. Proactively addressing these concerns is critical for the flourishing of ethical innovation and ensuring the long-term success of AI applications in healthcare.
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