Display omitted
► Modern synthetic chemistry techniques enable the efficient construction of fluorophores. ► Controlling dye properties with enzymes or light facilitates advanced imaging experiments. ...► Specific fluorophore labeling is achieved through orthogonal chemical reactions inside cells.
Small molecule fluorophores are essential tools for chemical biology. A benefit of synthetic dyes is the ability to employ chemical approaches to control the properties and direct the position of the fluorophore. Applying modern synthetic organic chemistry strategies enables efficient tailoring of the chemical structure to obtain probes for specific biological experiments. Chemistry can also be used to activate fluorophores; new fluorogenic enzyme substrates and photoactivatable compounds with improved properties have been prepared that facilitate advanced imaging experiments with low background fluorescence. Finally, chemical reactions in live cells can be used to direct the spatial distribution of the fluorophore, allowing labeling of defined cellular regions with synthetic dyes.
Because overall cranial morphology-biomechanics linkage in carnivorans is significantly influenced by both feeding and non-feeding ecological variables, whole-skull mechanical performance measures ...may be less sensitive to feeding ecology than regional characteristics within the skull. The temporomandibular joint could be one regional characteristic that is highly sensitive to feeding ecology considering that this joint is used in prey capture, food processing, and experiences compressive loading during mastication. Through 3D model construction, 3D printing, and compression tests, morphological and mechanical performance measures were determined for the temporomandibular joint trabecular bone structure of 40 species representative of the phylogenetic and ecology diversity of Carnivora. Remarkably, the results indicate that relative fill volume, relative structural complexity, elastic modulus, and relative maximum compressive strength of trabecular bone structure are not significantly related to phylogeny or ecology. The results reveal that morphological and mechanical performance attributes of trabecular bone structure are primarily influenced by body size, and that positive centroid size allometry and positive body mass allometry are present for structural complexity. The lack of feeding ecological signal in dorso-ventral compressive loading of temporomandibular joint models indicates that carnivoran temporomandibular joint trabecular structures may not undergo significant differential remodeling as an evolutionary response to different mechanically demanding feeding tasks.
Cancer cells arise from normal cells through the acquisition of a series of mutations in oncogenes and tumour suppressor genes. Mouse models of human cancer often rely on germline alterations that ...activate or inactivate genes of interest. One limitation of this approach is that germline mutations might have effects other than somatic mutations, owing to developmental compensation. To model sporadic cancers associated with inactivation of the retinoblastoma (RB) tumour suppressor gene in humans, we have produced a conditional allele of the mouse Rb gene. We show here that acute loss of Rb in primary quiescent cells is sufficient for cell cycle entry and has phenotypic consequences different from germline loss of Rb function. This difference is explained in part by functional compensation by the Rb-related gene p107. We also show that acute loss of Rb in senescent cells leads to reversal of the cellular senescence programme. Thus, the use of conditional knockout strategies might refine our understanding of gene function and help to model human cancer more accurately.
Small molecules are important tools to measure and modulate intracellular signaling pathways. A longstanding limitation for using chemical compounds in complex tissues has been the inability to ...target bioactive small molecules to a specific cell class. Here, we describe a generalizable esterase–ester pair capable of targeted delivery of small molecules to living cells and tissue with cellular specificity. We used fluorogenic molecules to rapidly identify a small ester masking motif that is stable to endogenous esterases, but is efficiently removed by an exogenous esterase. This strategy allows facile targeting of dyes and drugs in complex biological environments to label specific cell types, illuminate gap junction connectivity, and pharmacologically perturb distinct subsets of cells. We expect this approach to have general utility for the specific delivery of many small molecules to defined cellular populations.
The choice of reconstruction type is of utmost importance in treating breast cancer. There are two major reconstructive pathways in this group of patients: autologous breast reconstruction (ABR) and ...implant-based breast reconstruction (IBR). The aim of this systematic review and meta-analysis was to assess and compare IBR vs. ABR.
A review of studies reporting the differences between the procedures was performed. The MEDLINE/PubMed, ScienceDirect, EMBASE, BIOSIS, SciELO, Scopus, and Web of Science databases were thoroughly searched in September 2021. The data concerning group characteristics, BREAST-Q scores, complication rates, length of stay (LOS), and costs were extracted. The Cochrane risk-of-bias tool was used for randomized studies, while Newcastle–Ottawa Quality Assessment for Cohort Studies was used for other types of research.
Our meta-analysis included 32 studies (n = 55,455). We observed significantly better outcomes following ABR when it comes to esthetic satisfaction (mean difference MD -8.51; 95% confidence interval CI -10.70, -6.33; p<0.001) and satisfaction with the entire reconstructive treatment (MD -6.56; 95% CI -9.97, -3.14; p<0.001). Both methods appeared to be comparable in terms of safety, while the complication rates varied insignificantly between the groups (odds ratio OR 1.06; 95% CI 0.71, 1.59; p = 0.76). ABR seems to be correlated with significantly higher costs (standard mean difference SMD -0.69; 95% CI -1.21, -0.17; p = 0.010).
The results obtained from this evidence-based study will improve the understanding of the different clinical pathways that patients can be assigned to. The study emphasized the advantages and disadvantages of both methods.
Background
The aim of this study was to assess the usefulness of protective negative-pressure wound therapy (NPWT) in the reduction of wound healing complications (WHC) and surgical site infections ...(SSI) after diverting ileostomy closure in patients who underwent surgery for colorectal cancer.
Methods
In this prospective randomized clinical trial in a tertiary academic surgical center, patients who had colorectal cancer surgery with protective loop ileostomy and were scheduled to undergo ileostomy closure with primary wound closure from January 2016 to December 2018 were randomized to be treated with or without NPWT. The primary endpoint was the incidence of WHC. Secondary endpoints were incidence of SSI, length of postoperative hospital stay (LOS), and length of complete wound healing (CWH) time.
Results
We enrolled 35 patients NPWT (24 males 68.6%; mean age 61.6 ± 11.3 years), with NPWT and 36 patients (20 males 55.6%; mean age 62.4 ± 11.3 years) with only primary wound closure (control group). WHC was observed in 11 patients (30.6%) in the control group and 3 (8.57%) in the NPWT group (
p
= 0.020). Patients in the NPWT group had a significantly lower incidence of SSI (2 5.71% vs. 8 22.2% in the control group;
p
= 0.046) as well as significantly shorter median CWH (7 7–7 days vs. 7 7–15.5 days,
p
= 0.030). There was no difference in median LOS between groups (3 2.5–5 days in the control group vs. 4 2–4 days in the NPWT group;
p
= 0.072).
Conclusions
Prophylactic postoperative NPWT after diverting ileostomy closure in colorectal cancer patients reduces the incidence of WRC and SSI.
Clinical trial registration
clinicaltrials.gov (NCT04088162).
Despite the apparent simplicity of the xanthene fluorophores, the preparation of caged derivatives with free carboxy groups remains a synthetic challenge. A straightforward and flexible strategy for ...preparing rhodamine and fluorescein derivatives was developed using reduced, “leuco” intermediates.
Despite the superb fossil record of the saber-toothed cat, Smilodon fatalis, ontogenetic age determination for this and other ancient species remains a challenge. The present study utilizes a new ...technique, a combination of data from stable oxygen isotope analyses and micro-computed tomography, to establish the eruption rate for the permanent upper canines in Smilodon fatalis. The results imply an eruption rate of 6.0 millimeters per month, which is similar to a previously published average enamel growth rate of the S. fatalis upper canines (5.8 millimeters per month). Utilizing the upper canine growth rate, the upper canine eruption rate, and a previously published tooth replacement sequence, this study calculates absolute ontogenetic age ranges of tooth development and eruption in S. fatalis. The timing of tooth eruption is compared between S. fatalis and several extant conical-toothed felids, such as the African lion (Panthera leo). Results suggest that the permanent dentition of S. fatalis, except for the upper canines, was fully erupted by 14 to 22 months, and that the upper canines finished erupting at about 34 to 41 months. Based on these developmental age calculations, S. fatalis individuals less than 4 to 7 months of age were not typically preserved at Rancho La Brea. On the whole, S. fatalis appears to have had delayed dental development compared to dental development in similar-sized extant felids. This technique for absolute ontogenetic age determination can be replicated in other ancient species, including non-saber-toothed taxa, as long as the timing of growth initiation and growth rate can be determined for a specific feature, such as a tooth, and that growth period overlaps with the development of the other features under investigation.
Although there are examples of museums that use cutting-edge techniques and technologies to facilitate inclusive learning environments, very little is known about the extent that natural history ...museums have implemented inclusive education practices. The current study examines data from two cross-sectional surveys; a survey of museum education directors and a survey of museum executive directors. The results indicate that a wide variety of inclusive education techniques and services are used by museums. However, progress still needs to be made overall; especially when it comes to offering more accessible learning opportunities to visitors who have visual impairments. The natural history museums of the United States of America have noteworthy and distinctive learning opportunities to offer society, but it is clear that financial restrictions, constraints from older infrastructure, and museum education staff shortages are factors that have hindered some museums' efforts to create learning environments that are more inclusive.
The utility of small molecules to probe or perturb biological systems is limited by the lack of cell-specificity. “Masking” the activity of small molecules using a general chemical modification and ...“unmasking” it only within target cells overcomes this limitation. To this end, we have developed a selective enzyme–substrate pair consisting of engineered variants of E. coli nitroreductase (NTR) and a 2-nitro-N-methylimidazolyl (NM) masking group. To discover and optimize this NTR–NM system, we synthesized a series of fluorogenic substrates containing different nitroaromatic masking groups, confirmed their stability in cells, and identified the best substrate for NTR. We then engineered the enzyme for improved activity in mammalian cells, ultimately yielding an enzyme variant (enhanced NTR, or eNTR) that possesses up to 100-fold increased activity over wild-type NTR. These improved NTR enzymes combined with the optimal NM masking group enable rapid, selective unmasking of dyes, indicators, and drugs to genetically defined populations of cells.
PDF
