Exosomes are nanovesicles secreted by most cellular types that carry important biochemical compounds throughout the body with different purposes, playing a preponderant role in cellular ...communication. Because of their structure, physicochemical properties and stability, recent studies are focusing in their use as nanocarriers for different therapeutic compounds for the treatment of different diseases ranging from cancer to Parkinson's disease. However, current bioseparation protocols and methodologies are selected based on the final exosome application or intended use and present both advantages and disadvantages when compared among them. In this context, this review aims to present the most important technologies available for exosome isolation while discussing their advantages and disadvantages and the possibilities of being combined with other strategies. This is critical since the development of novel exosome‐based therapeutic strategies will be constrained to the effectiveness and yield of the selected downstream purification methodologies for which a thorough understanding of the available technological resources is needed.
Electrokinetically driven insulator‐based microfluidic devices represent an attractive option to manipulate particle suspensions. These devices can filtrate, concentrate, separate, or characterize ...micro and nanoparticles of interest. Two decades ago, inspired by electrode‐based dielectrophoresis, the concept of insulator‐based dielectrophoresis (iDEP) was born. In these microfluidic devices, insulating structures (i.e., posts, membranes, obstacles, or constrictions) built within the channel are used to deform the spatial distribution of an externally generated electric field. As a result, particles suspended in solution experience dielectrophoresis (DEP). Since then, it has been assumed that DEP is responsible for particle trapping in these devices, regardless of the type of voltage being applied to generate the electric field—direct current (DC) or alternating current. Recent findings challenge this assumption by demonstrating particle trapping and even particle flow reversal in devices that prevent DEP from occurring (i.e., unobstructed long straight channels stimulated with a DC voltage and featuring a uniform electric field). The theory introduced to explain those unexpected observations was then applied to conventional “DC‐iDEP” devices, demonstrating better prediction accuracy than that achieved with the conventional DEP‐centered theory. This contribution summarizes contributions made during the last two decades, comparing both theories to explain particle trapping and highlighting challenges to address in the near future.
Radioresistance of tumor cells gives rise to local recurrence and disease progression in many patients. MicroRNAs (miRNAs) are master regulators of gene expression that control oncogenic pathways to ...modulate the radiotherapy response of cells. In the present study, differential expression profiling assays identified 16 deregulated miRNAs in acquired radioresistant breast cancer cells, of which miR‐122 was observed to be up‐regulated. Functional analysis revealed that miR‐122 has a role as a tumor suppressor in parental cells by decreasing survival and promoting radiosensitivity. However, in radioresistant cells, miR‐122 functions as an oncomiR by promoting survival. The transcriptomic landscape resulting from knockdown of miR‐122 in radioresistant cells showed modulation of the ZNF611, ZNF304, RIPK1, HRAS, DUSP8 and TNFRSF21 genes. Moreover, miR‐122 and the set of affected genes were prognostic factors in breast cancer patients treated with radiotherapy. Our data indicate that up‐regulation of miR‐122 promotes cell survival in acquired radioresistant breast cancer and also suggest that miR‐122 differentially controls the response to radiotherapy by a dual function as a tumor suppressor an and oncomiR dependent on cell phenotype.
Radiotherapy exerts cytotoxic effects on primary tumor cells; nevertheless, some tumor cells eventually develop radioresistance via molecular reprogramming to acquire the ability to survive. miR‐122 has been categorized as a tumor suppressor in breast cancer. Here, we report a novel function of miR‐122 as an oncomiR in radioresistant breast cancer cells. OncomiR‐122 is essential to maintain the survival of radioresistant breast cancer cells via the control of a network of survival genes.
A
bstract
The unpolarised transverse momentum dependent distribution and fragmentation functions are extracted from HERMES and COMPASS experimental measurements of SIDIS multiplicities for charged ...hadron production. The data are grouped into independent bins of the kinematical variables, in which the TMD factorisation is expected to hold. A simple factorised functional form of the TMDs is adopted, with a Gaussian dependence on the intrinsic transverse momentum, which turns out to be quite adequate in shape. HERMES data do not need any normalisation correction, while fits of the COMPASS data much improve with a
y
-dependent overall normalisation factor. A comparison of the extracted TMDs with previous EMC and JLab data confirms the adequacy of the simple Gaussian distributions. The possible role of the TMD evolution is briefly considered.
Exosomes are small extracellular vesicles that can be obtained from several body fluids such as blood and urine. Since these vesicles can carry biomarkers and other cargo, they have application in ...healthcare diagnostics and therapeutics, such as liquid biopsies and drug delivery. Yet, their identification and separation from a sample remain challenging due to their high degree of heterogeneity and their co‐existence with other bioparticles. In this contribution, we review the state‐of‐the‐art on electrical techniques and methods to displace, selectively trap/isolate, and detect/characterize exosomes in microfluidic devices. Although there are many reviews focused on exosome separation using benchtop equipment, such as ultracentrifugation, there are limited reviews focusing on the use of electrical phenomena in microfluidic devices for exosome manipulation and detection. Here, we highlight contributions published during the past decade and present perspectives for this research field for the near future, outlining challenges to address in years to come.
'Speed breeding' (SB) shortens the breeding cycle and accelerates crop research through rapid generation advancement. SB can be carried out in numerous ways, one of which involves extending the ...duration of plants' daily exposure to light, combined with early seed harvest, to cycle quickly from seed to seed, thereby reducing the generation times for some long-day (LD) or day-neutral crops. In this protocol, we present glasshouse and growth chamber-based SB approaches with supporting data from experimentation with several crops. We describe the conditions that promote the rapid growth of bread wheat, durum wheat, barley, oat, various Brassica species, chickpea, pea, grass pea, quinoa and Brachypodium distachyon. Points of flexibility within the protocols are highlighted, including how plant density can be increased to efficiently scale up plant numbers for single-seed descent (SSD). In addition, instructions are provided on how to perform SB on a small scale in a benchtop growth cabinet, enabling optimization of parameters at a low cost.
Transposable elements (TEs) are major components of large plant genomes and main drivers of genome evolution. The most recent assembly of hexaploid bread wheat recovered the highly repetitive TE ...space in an almost complete chromosomal context and enabled a detailed view into the dynamics of TEs in the A, B, and D subgenomes.
The overall TE content is very similar between the A, B, and D subgenomes, although we find no evidence for bursts of TE amplification after the polyploidization events. Despite the near-complete turnover of TEs since the subgenome lineages diverged from a common ancestor, 76% of TE families are still present in similar proportions in each subgenome. Moreover, spacing between syntenic genes is also conserved, even though syntenic TEs have been replaced by new insertions over time, suggesting that distances between genes, but not sequences, are under evolutionary constraints. The TE composition of the immediate gene vicinity differs from the core intergenic regions. We find the same TE families to be enriched or depleted near genes in all three subgenomes. Evaluations at the subfamily level of timed long terminal repeat-retrotransposon insertions highlight the independent evolution of the diploid A, B, and D lineages before polyploidization and cases of concerted proliferation in the AB tetraploid.
Even though the intergenic space is changed by the TE turnover, an unexpected preservation is observed between the A, B, and D subgenomes for features like TE family proportions, gene spacing, and TE enrichment near genes.
Temperature is a critical—yet sometimes overlooked—parameter in microfluidics. Microfluidic devices can experience heating inside their channels during operation due to underlying physicochemical ...phenomena occurring therein. Such heating, whether required or not, must be monitored to ensure adequate device operation. Therefore, different techniques have been developed to measure and control temperature in microfluidic devices. In this contribution, the operating principles and applications of these techniques are reviewed. Temperature‐monitoring instruments revised herein include thermocouples, thermistors, and custom‐built temperature sensors. Of these, thermocouples exhibit the widest operating range; thermistors feature the highest accuracy; and custom‐built temperature sensors demonstrate the best transduction. On the other hand, temperature control methods can be classified as external‐ or integrated‐methods. Within the external methods, microheaters are shown to be the most adequate when working with biological samples, whereas Peltier elements are most useful in applications that require the development of temperature gradients. In contrast, integrated methods are based on chemical and physical properties, structural arrangements, which are characterized by their low fabrication cost and a wide range of applications. The potential integration of these platforms with the Internet of Things technology is discussed as a potential new trend in the field.
We present new weak-lensing observations of 1E 0657-558 (z = 0.296), a unique cluster merger, that enable a direct detection of dark matter, independent of assumptions regarding the nature of the ...gravitational force law. Due to the collision of two clusters, the dissipationless stellar component and the fluid-like X-ray-emitting plasma are spatially segregated. By using both wide-field ground-based images and HST/ACS images of the cluster cores, we create gravitational lensing maps showing that the gravitational potential does not trace the plasma distribution, the dominant baryonic mass component, but rather approximately traces the distribution of galaxies. An 8 ssignificance spatial offset of the center of the total mass from the center of the baryonic mass peaks cannot be explained with an alteration of the gravitational force law and thus proves that the majority of the matter in the system is unseen.
PDF
