Numbed Cell

This image is the three-layer overlay image of the differentiated mouse odontoblasts taken from confocal microscope located in UIC medical school. The first layer is the blue color stained nuclei; the second layer is the green color immunostained tublin which represents the cellular skeleton; the third layer is the red color immunostained numb protein. The overlay clearly indicated the physical locations of the numb protein in the cell. Numb has been shown to play critical roles in maintaining the stem cell property in neurons, and we are very excited to identify numb expression in odontoblasts. This discovery may help me to elude the mystery of tooth development

An Integrated Process Analytical Technology (PAT) Approach for Pharmaceutical Crystallization Process Understanding to Ensure Product Quality and Safety: FDA Scientist’s Perspective

In this review, a brief overview of the current regulatory science framework pertinent to pharmaceutical crystallization and process characterization is made first. The FDA’s scientific research on pharmaceutical crystallization process understanding and product characterization is then illustrated via several aspects: (1) Combined real-time PAT monitoring and process chemometrics for mapping the state of a pharmaceutical crystallization process; (2) Combined real-time PAT process monitoring and first-principle modeling for elucidating the nucleation mechanisms of a dynamic pharmaceutical crystallization process; (3) Combined real-time PAT process monitoring, Design of Experiments (DOE), and General Linear Modeling (GLM) to establish a hybrid approach for process characterization and process design space development; and (4) Integrated PAT approach for nucleation induction time measurement. Finally, some of the current challenges and future outlook on pharmaceutical crystallization process and product characterization across the pipeline, from drug substance to drug product development, manufacturing, and process scale-up to ensure product quality and safety, and ultimately to protect and promote public health is discussed from both a regulatory science and process engineering point of view

Oxidative Dehydrogenative [2 + 3]-Cyclization of Glycine Esters with Aziridines Leading to Imidazolidines

Oxidative dehydrogenative [2 + 3]-cyclization of glycine derivatives with <i>N</i>-sulfonylaziridines is described. A series of complex imidazolidines were produced under mild and simple reaction conditions. A mechanism involving an unusual acid-promoted auto-oxidation is proposed

Table_1_Assessing larval fish diversity and conservation needs in the Luzon strait using DNA barcoding.xlsx

IntroductionAccurate species identification and biodiversity assessment of larval fish are essential for effective management and conservation of fisheries resources, as it allows for the estimation of parent stocks, assessment of future recruitment, and prediction of spawning and nursing grounds. However, traditional morphology-based identification methods have inherent limitations, highlighting the need for accurate and efficient techniques to address these challenges effectively. The Luzon Strait, a crucial channel connecting the South China Sea to Western Pacific Ocean, is renowned for its fish biodiversity. However, our knowledge of the biodiversity status of larval fish species in this region remains insufficient.MethodsHere we employed DNA barcoding to assess larval fish species diversity in the Luzon Strait and adjacent waters. We investigated the species composition, diversity, and geographical distribution of larval fish communities in the region. Moreover, we assessed habitat types, human uses, and IUCN conservation status of each larval fish species.ResultsA total of 385 larval fish individuals were collected from 15 stations, and 354 individuals were successfully barcoded and identified, representing 147 species from 93 genera, 44 families, and 22 orders. The interspecific Kimura 2-parameter (K2P) divergence exhibited a significant increase of approximately 55-fold higher than intraspecific divergence. The phylogenetic neighbor-joining tree confirmed the distinct lineages for each taxonomic level, demonstrating the feasibility of DNA barcoding. We observed notable variations in fish species diversity and community composition among sampling stations. Non-metric multidimensional scaling analysis revealed greater diversity and dissimilarity of larval fish community compositions in the western regions compared to the eastern regions. This pattern corresponded to the grouping based on the path of the Kuroshio current, suggesting its influence on the fish community structure. Additionally, economically valuable species were identified at these stations, highlighting their ecological significance as potential spawning or nursery grounds for larval fish. We also examined the habitat type, human use, and conservation status of each larval fish species, providing comprehensive insights into their ecological significance and conservation needs.DiscussionThe establishment of a local DNA sequences database through DNA barcoding will greatly enhance the accuracy of species identification in environmental DNA (eDNA) metabarcoding applications. Altogether, this study offers valuable information for identifying important spawning and nursing grounds of fish populations, thereby supporting sustainable management and conservation of fisheries resources in this region.</p

Influence of <i>In-Situ</i> Oil Sands Development on Caribou (<i>Rangifer tarandus</i>) Movement

<div><p>In-situ oil sands development (ISD) involves a network of facilities, wells, roads and pipelines to extract and transport subsurface bitumen. This technology is rapidly expanding and there is uncertainty whether ISDs restrict animal movement, leading to increased extinction probabilities for some wide-ranging species. Here we test for effects of simulated future (i.e., 50 years from now) and current ISDs on simulated movements of woodland caribou (<i>Rangifer tarandus</i>), a threatened species across North America. In simulations of future scenarios, we varied the spacing and permeability of ISDs and the presence/absence of protected areas. Permeability was measured as the number of times simulated caribou crossed ISDs with different levels of modelled permeability. We estimated the effects of these factors on caribou step length and annual home range size, key metrics of small and large spatiotemporal scales of movement, respectively. Current caribou crossings of above-ground pipeline features of ISDs were measured using camera traps and compared to expected caribou crossing rates based on present-day caribou movement simulations. Current crossing rates were evaluated within the context of predicted future crossing success rates necessary to maintain caribou step lengths and home ranges. With few exceptions, permeability across ISDs was the main factor affecting caribou movement, more so than spacing between developments or the presence of protected areas. However, minimal permeability (crossing rates of c. 15% to 60%, relative to an undisturbed site was needed to maintain existing home range size and step lengths. The effect of permeability on home range size and step length was non-linear, suggesting that small increases in permeability would provide a disproportionately greater benefit to caribou movement. Our predictions demonstrate that maintaining permeability across ISDs is more important than spacing between leases or including protected areas, and thus provides clear direction for mitigation efforts for features that will exist on the landscape for decades to come.</p></div

Chemical structures of Celastrol.

<p>Celastrol is a natural triterpenoid quinone methide isolated from the Chinese plant genuses of celastrus, maytenus, and tripterygium.</p

Pulmonary artery perfusion with TNF-α Ab reduced CPB-induced Evens blue leakage in lung.

<p>Group I: CPB+LPD; Group II: CPB+TNF-α Ab; Group III: CPB only; Group IV: Open chest no CPB. Evans blue (2%) was injected intravenously in rabbits one hour after CPB or the chest was kept open. Evans blue dye leaked into the lungs was extracted according to the description in the Methods. The Evans blue permeability rate (µg/g lung tissue) was calculated according to this equation: Evans blue concentration (µg/mL)×volume of formamide (ml) ÷ the total lung weight (g). n = 3. Data were presented as mean ± SE. ^aP<0.05, group VI vs. group I, II, and III. ^bP<0.05, group II vs. group I and III.</p

Celastrol inhibited constitutively active NF-kB in LP-1 MM cells.

<p>An altered subcellular distribution of NF-κb was observed. LP-1 cells were incubated with medium (A), 1 µM celastrol for 30 min (B), 1 µM Zinc Protoporphyrin-9 (ZnPPIX) (C), 1 µM celastrol combined with 1 µM ZnPPIX (D) and then analysed for the intracellular distribution of p65 by fluorescence microscope. Green indicates p65, and blue indicates nuclei (original magnification ×400). The results shown are representative of three independent experiments.</p

Validation of binding of TNF-α Ab to rabbit TNF-α and the functional blocking activity of the antibody.

<p><b>A</b>. Incubation with TNF-α Ab significantly reduced TNF-α level in rabbit plasma. TNF-α Ab (120 pg) bound on Protein A beads or BSA blocked beads was incubated with 100 µl of the supernatant of rabbit plasma for 30 min at 37°C. TNF-α level was then measured by ELISA. ^aP<0.05, students’ t-test. <b>B</b>. TNF-α Ab significantly decreased TNF-α-induced apoptosis in HUVEC. HUVEC on 96 well plate were treated with 1200 pg/ml TNF-α Ab only, 20 ng/ml human recombinant TNF-α only, or TNF-α Ab+TNF-α for 24 h. MTT assay was then performed to estimate HUVEC apoptosis. n = 3. Data were presented as mean ± SE.^aP<0.05, TNF-α only vs. control and TNF-α Ab only. ^bP<0.05, TNF-α Ab+TNF-α vs. TNF-α only.</p

In-situ oil sands development scenarios simulated to test development effects on caribou movement, showing <i>in-situ</i> oil sands developments with a 2-km buffer between projects.

<p>In-situ oil sands development scenarios simulated to test development effects on caribou movement, showing <i>in-situ</i> oil sands developments with a 2-km buffer between projects.</p