Cell Length Growth in the Fission Yeast Cell Cycle: Is It (Bi)linear or (Bi)exponential?

Fission yeast is commonly used as a model organism in eukaryotic cell growth studies. To describe the cells’ length growth patterns during the mitotic cycle, different models have been proposed previously as linear, exponential, bilinear and biexponential ones. The task of discriminating among these patterns is still challenging. Here, we have analyzed 298 individual cells altogether, namely from three different steady-state cultures (wild-type, wee1-50 mutant and pom1Δ mutant). We have concluded that in 190 cases (63.8%) the bilinear model was more adequate than either the linear or the exponential ones. These 190 cells were further examined by separately analyzing the linear segments of the best fitted bilinear models. Linear and exponential functions have been fitted to these growth segments to determine whether the previously fitted bilinear functions were really correct. The majority of these growth segments were found to be linear; nonetheless, a significant number of exponential ones were also detected. However, exponential ones occurred mainly in cases of rather short segments (<40 min), where there were not enough data for an accurate model fitting. By contrast, in long enough growth segments (≥40 min), linear patterns highly dominated over exponential ones, verifying that overall growth is probably bilinear.

Dynamic Polarization of Rab11a Modulates Crb2a Localization and Impacts Signaling to Regulate Retinal Neurogenesis

Interkinetic nuclear migration (IKNM) is the process in which pseudostratified epithelial nuclei oscillate from the apical to basal surface and in phase with the mitotic cycle. In the zebrafish retina, neuroepithelial retinal progenitor cells (RPCs) increase Notch activity with apical movement of the nuclei, and the depth of nuclear migration correlates with the probability that the next cell division will be neurogenic. This study focuses on the mechanisms underlying the relationships between IKNM, cell signaling, and neurogenesis. In particular, we have explored the role IKNM has on endosome biology within RPCs. Through genetic manipulation and live imaging in zebrafish, we find that early (Rab5-positive) and recycling (Rab11a-positive) endosomes polarize in a dynamic fashion within RPCs and with reference to nuclear position. Functional analyses suggest that dynamic polarization of recycling endosomes and their activity within the neuroepithelia modulates the subcellular localization of Crb2a, consequently affecting multiple signaling pathways that impact neurogenesis including Notch, Hippo, and Wnt activities. As nuclear migration is heterogenous and asynchronous among RPCs, Rab11a-affected signaling within the neuroepithelia is modulated in a differential manner, providing mechanistic insight to the correlation of IKNM and selection of RPCs to undergo neurogenesis.

Targeted micelles with chemotherapeutics and gene drugs to inhibit the G1/S and G2/M mitotic cycle of prostate cancer

Background Chemotherapy and gene therapy are used in clinical practice for the treatment of castration-resistant prostate cancer. However, the poor efficiency of drug delivery and serious systemic side effects remain an obstacle to wider application of these drugs. Herein, we report newly designed PEO-PCL micelles that were self-assembled and modified by spermine ligand, DCL ligand and TAT peptide to carry docetaxel and anti-nucleostemin siRNA. Results The particle size of the micelles was 42 nm, the zeta potential increased from − 12.8 to 15 mV after grafting with spermine, and the optimal N/P ratio was 25:1. Cellular MTT experiments suggested that introduction of the DCL ligand resulted in high toxicity toward PSMA-positive cells and that the TAT peptide enhanced the effect. The expression of nucleostemin was significantly suppressed in vitro and in vivo, and the tumour-inhibition experiment showed that the dual-drug delivery system suppressed CRPC tumour proliferation. Conclusions This targeted drug delivery system inhibited the G1/S and G2/M mitotic cycle via synergistic interaction of chemotherapeutics and gene drugs.

The application of 1.8-naphthalic anhydride to control ALS-herbicide resistant barnyardgrass with graminicides

Goal. Investigate the possibility to use 1,8-naphthalic anhydride metabolism inductor to control acetolactate synthase (ALS) inhibitor-resistant biotype of common graminicides of aryloxyphenoxypropionic acid class in rice. Methodology. The interaction of 1,8-naphthalic anhydride and fenoxaprop-p-ethyl on variety Vikont rice plants was studied under laboratory aseptic conditions. The data were statistically processed. Results. In Ukraine we have identified the biotype of resistant to herbicide ALS inhibitors Echinochloa crus-galli, which is cross-resistant to widely used herbicides — ALS inhibitors of the following chemical classes: imidazolinones (imazamox, imazapyr), sulfonylurea (nicosulfuron), triazolopyrimidines (penoxsulam). The possibilities of chemical control of weeds in rice, corn, sunflower, etc. crops are significantly limited. Multi-resistance of this weed biotype to herbicides — inhibitors of photosynthesis, mitotic cycle, 5-enolpyruvylshikimate-3-phosphate synthase, acetyl-CoA-carboxylase, protein synthesis — has not been detected. Therefore, the use of graminicides of aryloxyphenoxypropionate class is promising for the control of this ALS-resistant biotype of Echinochloa crus-galli. To increase the selectivity of fenoxaprop-P-ethyl application to rice plants, we propose to treat the seeds of the crop with the inductor of xenobiotics metabolism in plants — 1.8-naphthalic anhydride before sowing. When using 1.8-naphthalic anhydride in concentrations of 10-5 M, phytotoxicity of fenoxaprop-P-ethyl in concentrations of 10-6 and 10-5 M to rice plants is effectively reduced. Conclusions. The use of 1.8-naphthalic anhydride is promising for increasing the selectivity of fenoxaprop-P-ethyl for rice plants and allows the development of technologies using graminicides of aryloxyphenoxypropionate class to control ALS-resistant biotype of Echinochloa crus-galli in crops. Also, it is necessary to pay attention to the problem of ALS-resistant weed biotype proliferation control in agrophytocenoses in regions of Ukraine.

Comparing DNA replication programs reveals large timing shifts at centromeres of endocycling cells in maize roots

ABSTRACTPlant cells undergo two types of cell cycles – the mitotic cycle in which DNA replication is coupled to mitosis, and the endocycle in which DNA replication occurs in the absence of cell division. To investigate DNA replication programs in these two types of cell cycles, we pulse labeled intact root tips of maize (Zea mays) with 5-ethynyl-2’-deoxyuridine (EdU) and used flow sorting of nuclei to examine DNA replication timing (RT) during the transition from a mitotic cycle to an endocycle. Here, we compare sequence-based RT profiles and found that most regions of the maize genome replicate at the same time during S phase in mitotic and endocycling cells, despite the need to replicate twice as much DNA in the endocycle. However, regions collectively corresponding to 2% of the genome displayed significant changes in timing between the two types of cell cycles. The majority of these regions are small, with a median size of 135 kb, and shift to a later RT in the endocycle. However, we found larger regions that shifted RT in centromeres of seven of the ten maize chromosomes. These regions covered the majority of the previously defined functional centromere in each case, which are ∼1–2 Mb in size in the reference genome. They replicate mainly during mid S phase in mitotic cells, but primarily in late S phase of the endocycle. Strikingly, the immediately adjacent pericentromere sequences are primarily late replicating in both cell cycles. Analysis of CENH3 enrichment levels in nuclei of different ploidies suggested that there is only a partial replacement of CENH3 nucleosomes after endocycle replication is complete. The shift to later replication of centromeres and reduced CENH3 enrichment after endocycle replication is consistent with the hypothesis that centromeres are being inactivated as their function is no longer needed.AUTHOR SUMMARYIn traditional cell division, or mitosis, a cell’s genetic material is duplicated and then split between two daughter cells. In contrast, in some specialized cell types, the DNA is duplicated a second time without an intervening division step, resulting in cells that carry twice as much DNA – a phenomenon called an endocycle, which is common during plant development. At each step, DNA replication follows an ordered program, in which highly compacted DNA is unraveled and replicated in sections at different times during the synthesis (S) phase. In plants, it is unclear whether traditional and endocycle programs are the same. Using root tips of maize, we found a small portion of the genome whose replication in the endocycle is shifted in time, usually to later in S phase. Some of these regions are scattered around the genome, and mostly coincide with active genes. However, the most prominent shifts occur in centromeres. This location is noteworthy because centromeres orchestrate the process of separating duplicated chromosomes into daughter cells, a function that is not needed in the endocycle. Our observation that centromeres replicate later in the endocycle suggests there is an important link between the time of replication and the function of centromeres.

The Improvement of Paclitaxel Cytotoxicity using Nanocellulose based Nature Resources

Paclitaxel is one of the cancer drugs that often used. These drug kills cancer cells byinhibiting mitotic cycle. The efficiency of paclitaxel is increased by the use ofnanomaterials as a carrier of paclitaxel. Nanomaterials can enhance encapsulationefficiency, improve the drug release to the target cell following nanomaterialdegradation, and improve local accumulation of drug in the cell through endocytosisreceptor. Nanomaterial that often used forencapsulation of paclitaxel is a polymerderived from natural resources such as cellulose. The advantages of cellulose as acarrier of paclitaxel are nontoxic, biodegradable, and very abundant from varioussources. One of the potential sources of cellulose for drug delivery system is cassavabaggase.Keywords: Paclitaxel, encapsulation, cell viability, nanocellulose