Miracle-dz/UniFAR-FTUs huggingface dataset:
Nile Red-Poly(Methyl Methacrylate)/Silica Nanocomposite Particles Increase the Sensitivity of Cervical Cancer Cells to Tamoxifen

Tamoxifen (TAM) is a hormonal drug and is mainly used as an anti-estrogen in breast cancer patients. TAM binds to estrogen receptors (ERs), resulting in inhibition of estrogen signaling pathways and thus, a downregulation of cell proliferation. Cancer cells with negative or low ER expression will not uptake TAM and will show low response. Poly (methyl methacrylate) (PMMA) nanoparticles were prepared using surfactant-free emulsion polymerization, then were loaded with Nile red (NR), which resulted in PMMA-NR. To enhance TAM delivery to cervical cancer cells (HELA), which is considered ER-negative, we loaded TAM and polymethyl methacrylate nanoparticles-Nile-red into silica (PMMA-NR-Si-TAM). The uptake and intracellular distribution were visualized by confocal laser scanning microscopy, and the in vitro cytotoxic activity was evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay using HELA and non-tumorigenic cell line HFF-1. The sensitivity of HELA (LC50: 207.31 µg/mL) and HFF-1 (LC50: 234.08 µg/mL) to free TAM was very low. However, after the encapsulation of TAM with PMMA-NR, the sensitivity significantly increased HELA (LC50: 71.83 µg/mL) and HFF-1 (LC50: 37.36 µg/mL). This indicates that TAM can be used for the treatment of ER-negative cervical cancer once conjugated to PMMA-NR nanoparticles. In addition, the PMMA-NR formulation appears to be highly suitable for cancer imaging and drug delivery.
PAK3 controls the tangential to radial migration switch of cortical interneurons by coordinating changes in cell shape and polarity

During the embryonic development, cortical interneurons migrate a long distance tangentially and then re-orient radially to settle in the cortical plate where they contribute to cortical circuits. Migrating interneurons express PAK3, a p21-activated kinase that switches between active and inactive states and controls interneuron migration by unknown mechanism(s). Here we examined the role of the kinase activity of PAK3 to regulate the migration of cortical interneurons. We showed that interneurons expressing a constitutively active PAK3 mutant (PAK3-ca) oriented preferentially radially in the cortex, extended short leading processes and exhibited unstable polarity. On the contrary, interneurons expressing an inactive PAK3 mutant (PAK3-kd for kinase dead) extended branched leading processes, showed directed nuclear movements and remained in the tangential pathways. Results showed that PAK3 kinase activity controls the switch between the tangential and radial modes of migration of cortical interneurons and identified myosin 2B as an effector of this switch.
The Addition of a Synthetic LPS-Targeting Domain Improves Serum Stability While Maintaining Antimicrobial, Antibiofilm, and Cell Stimulating Properties of an Antimicrobial Peptide

Multi-drug resistant (MDR) bacteria and their biofilms are a concern in veterinary and human medicine. Protegrin-1 (PG-1), a potent antimicrobial peptide (AMP) with antimicrobial and immunomodulatory properties, is considered a potential alternative for conventional antibiotics. AMPs are less stable and lose activity in the presence of physiological fluids, such as serum. To improve stability of PG-1, a hybrid peptide, SynPG-1, was designed. The antimicrobial and antibiofilm properties of PG-1 and the PG-1 hybrid against MDR pathogens was analyzed, and activity after incubation with physiological fluids was compared. The effects of these peptides on the IPEC-J2 cell line was also investigated. While PG-1 maintained some activity in 25% serum for 2 h, SynPG-1 was able to retain activity in the same condition for up to 24 h, representing a 12-fold increase in stability. Both peptides had some antibiofilm activity against Escherichia coli and Salmonella typhimurium. While both peptides prevented biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA), neither could destroy MRSA’s pre-formed biofilms. Both peptides maintained activity after incubation with trypsin and porcine gastric fluid, but not intestinal fluid, and stimulated IPEC-J2 cell migration. These findings suggest that SynPG-1 has much better serum stability while maintaining the same antimicrobial potency as PG-1.
Numerical Model for Formation and Evolution of the Bleb

The bleb morphology and its changes are an important mechanism of cell’s amoeboid migration. By releasing bonds between the membrane and the cortex of a cell, the formation of bleb can be observed experimentally, but the mechanism that affects the size and shape of this kind of bleb is waiting for further study. In this paper, a two-dimensional fluid-solid coupling model is established to describe a cell with membrane, cortex and cytoplasm in a solution, and a numerical solving method for the fluid-solid coupling model is developed to simulate the behaviors of cell bleb. The effects of parameters, such as the number of broken bonds, the viscosity coefficient of the cortex, and the cell’s membrane modulus on the size and the shape of the bleb were investigated. Numerical results show that the model is effective to simulate the formation and evolution of cell’s bleb, and derive the contribution of several affecting factors to the bleb shape and size clearly. SIGNIFICANCE To understand the process of cell migration with bleb pseudopods in the amoeba cell migration, it is necessary to study the formation mechanism of cells protruding bleb. In this paper, we propose a reasonable and reliable cell numerical model. With this model we successfully simulate the bleb phenomenon consistent with the experimental phenomenon by changing the key impact factors. The method in this paper is applicable to the cell model of amoeba cell migration pattern, which helps to understand the important role of blebs in the process of cell migration.
Cohesin-dockerin code in cellulosomal dual binding modes and its allosteric regulation by proline isomerization

Cellulose is the most abundant organic molecule on Earth and represents a renewable and practically everlasting feedstock for the production of biofuels and chemicals. Self-assembled owing to the high-affinity cohesin-dockerin interaction, cellulosomes are huge multi-enzyme complexes with unmatched efficiency in the degradation of recalcitrant lignocellulosic substrates. The recruitment of diverse dockerin-borne enzymes into a multicohesin protein scaffold dictates the three-dimensional layout of the complex, and interestingly two alternative binding modes have been proposed. Using single-molecule Fluorescence Resonance Energy Transfer, molecular dynamics simulations and NMR measurements on a range of cohesin-dockerin pairs, we directly detect varying distributions between these binding modes that follow a built-in cohesin-dockerin code. Surprisingly, we uncover a prolyl isomerase-modulated allosteric control mechanism, mediated by the isomerization state of a single proline residue, which regulates the distribution and kinetics of binding modes. Overall, our data provide a novel mechanistic understanding of the structural plasticity and dynamics of cellulosomes.
Long-term blood pressure variability, incidence of hypertension and changes in renal function in type 2 diabetes

Supplemental Digital Content is available in the text Objectives: Long-term visit-to-visit SBP variability (VVV) predicts cerebro-cardiovascular and renal events in patients with hypertension. Whether VVV predicts hypertension and/or chronic kidney disease is currently unknown. We assessed the role of VVV on the development of hypertension and changes in renal function in patients with type 2 diabetes and normal blood pressure (NBP) in a real-life clinical setting. Methods: Clinical records from 8998 patients with type 2 diabetes, NBP, and normal estimated glomerular filtration rate (eGFR) were analyzed. VVV was measured by SD of the mean SBP recorded in at least four visits during 2 consecutive years before follow-up. Hypertension was defined as SBP at least 140 mmHg and DBP at least 90 mmHg or the presence of antihypertensive treatment. Renal function was defined as worsening of albuminuria status and/or a reduction in eGFR at least 30% from baseline. Results: After a mean follow-up time of 3.5 ± 2.8 years, 3795 patients developed hypertension (12.1 per 100 person-years). An increase of 5 mmHg VVV was associated with a 19% (P < 0.0001) and a 5% (P = 0.008) independent increased risk of developing hypertension and worsening of albuminuria, respectively. We found no association between VVV and eGFR decrease from baseline. Patients with VVV in the upper quartile (>12.8 mmHg) showed a 50% increased risk of developing hypertension (P < 0.0001) and an almost 20% increased risk of worsening albuminuria (P = 0.004) as compared with those in the lower one (<6.9 mmHg). Conclusion: Increased VVV independently predicts incident hypertension and albuminuria worsening in type 2 diabetes and NBP.
Energy Consumption Evaluation of a Routing Protocol for Low-Power and Lossy Networks in Mesh Scenarios for Precision Agriculture

Sensor nodes are small, low-cost electronic devices that can self-organize into low-power networks and are susceptible to data packet loss, having computational and energy limitations. These devices expand the possibilities in many areas, like agriculture and urban spaces. In this work, we consider an IoT environment for monitoring a coffee plantation in precision agriculture. We investigate the energy consumption under low-power and lossy networks considering three different network topologies and an Internet Engineering Task Force (IETF) standardized Low-power and Lossy Network (LLN) routing protocol, the Routing Protocol for LLNs (RPL). For RPL, each secondary node selects a better parent according to some Objective Functions (OFs). We conducted simulations using Contiki Cooja 3.0, where we considered the Expected Transmission Count (ETX) and hop-count metric (HOP) metrics to evaluate energy consumption for three distinct topologies: tree, circular, and grid. The simulation results show that the circular topology had the best (lowest) energy consumption, being 15% better than the grid topology and 30% against the tree topology. The results help the need to improve the evolution of RPL metrics and motivate the network management of the topology.
Most of Tobacco Male Meiocytes Are Involved in Intercellular Nuclear Migration at the First Meiotic Prophase

Serial block-face scanning electron microscopy was used here to study tobacco male meiosis. Three-dimensional ultrastructural analyses revealed that intercellular nuclear migration (INM) occurs in 90–100% of tobacco meiocytes. At the very beginning of meiosis, every meiocyte connected with neighboring cells by more than 100 channels was capable of INM. At leptotene and zygotene, the nucleus in most tobacco meiocytes approached the cell wall and formed nuclear protuberances (NPs) that crossed the cell wall through the channels and got into the cytoplasm of a neighboring cell. The NPs did not separate from the migrating nuclei and never produced micronuclei. Approximately 70% of NPs reached nuclei of neighboring cells. The NPs and the nuclei they reached got very close, and the gap between their nuclear membranes became indistinguishable in some cases. At pachytene, NPs detached from the nuclei of neighboring cells and came back into their own cells. After that, the INM stopped. The reason for such behavior of nuclei is unclear. INM probably causes a short-lived fusion of two nuclei and thus has a potential to form aneuploid or unreduced pollen. We consider INM a normal part of tobacco meiosis.
Revisiting the carbon isotope discrimination and water use efficiency relation: the influence of mesophyll conductance

The carbon isotope discrimination (Δ) has been used widely to infer intrinsic water-use efficiency (iWUE) of C3 plants, a key parameter linking carbon and water fluxes. Despite the essential role of mesophyll conductance (gm) in photosynthesis and Δ, its effect on Δ-based predictions of iWUE has generally been neglected. Here, we derive a mathematical expression of iWUE as a function of Δ that includes gm (iWUEmes) and exploits the gm-stomatal conductance (gsc) relationship across drought-stress levels and plant functional groups (deciduous or semi-deciduous woody, evergreen woody and herbaceous species) in a global database. iWUEmes was further validated with an independent dataset of online-Δ and CO2 and H2O gas exchange measurements with seven species. Drought stress reduced gsc by 52% and gm by 45% averaged over all plant functional groups, but had no significant effect on the gsc/gm ratio, suggesting a well-constrained gsc/gm ratio of 0.79±0.07 (95%CI, n=198) across plant functional groups and drought-stress treatments. Due in part to the synchronous behavior of gsc and gm, gm was negatively correlated to iWUE. Incorporating the gsc/gm ratio in the iWUEmes model significantly improved the estimation of iWUE compared to the simple model. The inclusion of gm effects, even using a fixed gsc/gm ratio of 0.79 when gm is unknown, proved desirable to eliminate significant bias in estimating iWUE from Δ across various C3 vegetation types.
Transitions of Liver and Biliary Enzymes during Proton Beam Therapy for Hepatocellular Carcinoma

Proton beam therapy (PBT) is a curative treatment for hepatocellular carcinoma (HCC), because it can preserve liver function due to dose targeting via the Bragg peak. However, the degree of direct liver damage by PBT is unclear. In this study, we retrospectively analyzed liver/biliary enzymes and total bilirubin (T-Bil) as markers of direct liver damage during and early after PBT in 300 patients. The levels of these enzymes and bilirubin were almost stable throughout the treatment period. In patients with normal pretreatment levels, aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), and T-Bil were abnormally elevated in only 2 (1.2%), 1 (0.4%), 0, 2 (1.2%), and 8 (3.5%) patients, respectively, and in 8 of these 13 patients (61.5%) the elevations were temporary. In patients with abnormal pretreatment levels, the levels tended to decrease during PBT. GGT and T-Bil were elevated by 1.62 and 1.57 times in patients who received 66 Gy (RBE) in 10 fractions and 74 Gy (RBE) in 37 fractions, respectively, but again these changes were temporary. These results suggest that direct damage to normal liver caused by PBT is minimal, even if a patient has abnormal pretreatment enzyme levels.
Suppression of ABCE1-Mediated mRNA Translation Limits N-MYC–Driven Cancer Progression

These findings demonstrate that N-MYC–driven cancers are reliant on elevated rates of protein synthesis driven by heightened expression of ABCE1, a vulnerability that can be exploited through suppression of ABCE1. The ability of the N-MYC transcription factor to drive cancer progression is well demonstrated in neuroblastoma, the most common extracranial pediatric solid tumor, where MYCN amplification heralds a poor prognosis, with only 11% of high-risk patients surviving past 5 years. However, decades of attempts of direct inhibition of N-MYC or its paralogues has led to the conclusion that this protein is “undruggable. ” Therefore, targeting pathways upregulated by N-MYC signaling presents an alternative therapeutic approach. Here, we show that MYCN-amplified neuroblastomas are characterized by elevated rates of protein synthesis and that high expression of ABCE1, a translation factor directly upregulated by N-MYC, is itself a strong predictor of poor clinical outcome. Despite the potent ability of N-MYC in heightening protein synthesis and malignant characteristics in cancer cells, suppression of ABCE1 alone selectively negated this effect, returning the rate of translation to baseline levels and significantly reducing the growth, motility, and invasiveness of MYCN-amplified neuroblastoma cells and patient-derived xenograft tumors in vivo. The growth of nonmalignant cells or MYCN-nonamplified neuroblastoma cells remained unaffected by reduced ABCE1, supporting a therapeutic window associated with targeting ABCE1. Neuroblastoma cells with c-MYC overexpression also required ABCE1 to maintain cell proliferation and translation. Taken together, ABCE1-mediated translation constitutes a critical process in the progression of N-MYC–driven and c-MYC–driven cancers that warrants investigations into methods of its therapeutic inhibition. Significance: These findings demonstrate that N-MYC–driven cancers are reliant on elevated rates of protein synthesis driven by heightened expression of ABCE1, a vulnerability that can be exploited through suppression of ABCE1.
RNF219 interacts with CCR4–NOT in regulating stem cell differentiation

Regulation of RNA stability plays a crucial role in gene expression control. Deadenylation is the initial rate-limiting step for the majority of RNA decay events. Here, we show that RING Finger Protein 219 (RNF219) interacts with the CCR4-NOT deadenylase complex. RNF219-CCR4-NOT exhibits deadenylation activity in vitro. RNA-seq analyses identify some of the 2-cell specific genes and the neuronal genes significantly down-regulated upon RNF219 knockdown, while up-regulated after depletion of the CCR4-NOT subunit CNOT10 in mouse embryonic stem (ES) cells. RNF219 depletion leads to impaired neuronal lineage commitment during ES cell differentiation. Our study suggests that RNF219 is a novel interacting partner of CCR4-NOT, and required for maintenance of ES cell pluripotency.
0BINFORMATION CASCADES IN ENGINEERING DECISION-MAKING PROCESSES

UAbstractU: Conventional wisdom is that early involvement of stakeholders leads to better results in engineering decision-making processes. A commonly documented advantage of early stakeholder involvement is increased acceptance and ownership of the project by everyone involved, resulting in fewer disputes throughout the planning and decision-making process. However, information cascade theory suggests that early involvement and development of close working relationships among stakeholders may decrease a group’s ability to objectively and effectively evaluate engineering alternatives, as group members substitute the consensus of the group for their personal judgments. Additionally, innovation in design may be inversely correlated with the extent of group collaboration prior to selection of a preferred alternative. Experience in river engineering projects of the U.S. Bureau of Reclamation on the Rio Grande in New Mexico supports the idea that early stakeholder involvement, while effective in reducing disputes, has a suppressive effect on design innovation. Collaborative processes are intended to reach decisions with the benefit of the participants’ diverse viewpoints and expertise. Interactions of the decisionmaking group should be structured to maximize disclosure of relevant information and encourage each participant to perform an independent, objective evaluation before consensus is reached, thereby ensuring that the intent of a collaborative process—that the group receives the full benefit of each member’s knowledge—is achieved.
An exceptionally well preserved new species of ostracod (Crustacea) with soft parts in Baltic amber

Abstract A well-preserved ostracod in Baltic amber has been analysed with noninvasive methods by synchrotron radiation. A micro-tomographic image stack was prepared. The appendages are visualised as images and drawings are based on photographs of different images planes provided. The result is a description of a new species, Cypria kempfi, from the Eocene of Northern Germany. The way the fossilisation of this aquatic animal may have occurred is discussed. The possible ecological preferences of the species are considered.
Translating insights from the seed metabolome into improved prediction for healthful compounds in oat (Avena sativa L.)

Oat (Avena sativa L.) seed is a rich resource of beneficial lipids, soluble fiber, protein, and antioxidants, and is considered a healthful food for humans. Despite these characteristics, little is known regarding the genetic controllers of variation for these compounds in oat seed. We sought to characterize natural variation in the mature seed metabolome using untargeted metabolomics on 367 diverse lines and leverage this information to improve prediction for seed quality traits. We used a latent factor approach to define unobserved variables that may drive covariance among metabolites. One hundred latent factors were identified, of which 21% were enriched for compounds associated with lipid metabolism. Through a combination of whole-genome regression and association mapping, we show that latent factors that generate covariance for many metabolites tend to have a complex genetic architecture. Nonetheless, we recovered significant associations for 23% of the latent factors. These associations were used to inform a multi-kernel genomic prediction model, which was used to predict seed lipid and protein traits in two independent studies. Predictions for eight of the 12 traits were significantly improved compared to genomic best linear unbiased prediction when this prediction model was informed using associations from lipid-enriched factors. This study provides new insights into variation in the oat seed metabolome and provides genomic resources for breeders to improve selection for health-promoting seed quality traits. More broadly, we outline an approach to distill high-dimensional ‘omics’ data to a set of biologically-meaningful variables and translate inferences on these data into improved breeding decisions.
Decomposition and colonization by micro-arthropods of two litter types in a tropical montane rain forest in southern Ecuador

Abstract: The decomposition of litter of two tree species Graffenrieda emarginata (Melastomataceae), Purdiaea nutans (Cyrillaceae) and the mixture of both was investigated in a tropical montane rain forest in southern Ecuador at two different altitudes (1850 and 2280 m). The two litter types differed strongly in nitrogen concentration, suggesting that G. emarginata (1.21% N) decomposes faster than P. nutans (0.73% N). To study the effect of soil micro-arthropods on the decomposition process, litterbags with mesh-size of 48 μm, excluding soil micro-arthropods, and 1 mm, allowing colonization by soil micro-arthropods, were used. Litter mass loss was measured after 2, 6 and 12 mo exposure in the field; further, microbial biomass and micro-arthropod colonization of the litter were investigated after 2 and 12 mo. Generally, litter decomposed faster at 1850 m than at 2280 m (60% and 76% dry mass remaining after 12 mo, respectively); G. emarginata and mixed litter decomposed faster than P. nutans litter. After 12 mo mixed litter decomposed faster (65% of dry mass remaining) than both individual litter species (70% and 71% of dry mass of G. emarginata and P. nutans litter remaining, respectively) indicating that non-additive effects contributed to litter decomposition. Microbial biomass increased during the experiment and was higher at 1850 m than at 2280 m. The most abundant micro-arthropods in both litter types were oribatid mites followed by Collembola, Gamasina, Uropodina and Prostigmata + Astigmata. Micro-arthropods were generally more abundant at 1850 m suggesting higher biotic activity at lower altitudes. Soil micro-arthropods contributed little to decomposition processes indicating that litter decomposition is mainly due to micro-organisms.