Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of gap junction communication in alveolar epithelial cells by 18α-glycyrrhetinic acid.

Cultured alveolar epithelial cells exhibit gap junction intercellular communication (GJIC) and express regulated levels of connexin (Cx) 43 mRNA and protein. Newly synthesized radiolabeled Cx43 protein equilibrates with phosphorylated Cx43 isoforms; these species assemble to form both connexons and functional gap junction plaques. The saponin 18α-glycyrrhetinic acid (GA) rapidly and reversibly blocks GJIC at low concentrations (5 μM). Extended exposure to 18α-GA at higher concentrations causes inhibition of GJIC and time- and dose-dependent reductions in both Cx43 protein and mRNA expression. The latter toxic effects are paralleled by disassembly of gap junction plaques and are reversed less readily than acute effects on GJIC. These observations demonstrate 18α-GA-sensitive regulation of intercellular communication in epithelial cells from the mammalian lung and suggest a role for Cx43 expression and phosphorylation in acute and chronic regulation of GJIC between alveolar epithelial cells.
Candida–Epithelial Interactions

A plethora of intricate and dynamic molecular interactions occur between microbes and the epithelial cells that form the mucosal surfaces of the human body. Fungi, particularly species of Candida, are commensal members of our microbiota, continuously interacting with epithelial cells. Transient and localised perturbations to the mucosal environment can facilitate the overgrowth of fungi, causing infection. This minireview will examine the direct and indirect mechanisms by which Candida species and epithelial cells interact with each other, and explore the factors involved in the central processes of adhesion, invasion, and destruction of host mucosal surfaces.
Effects of hindlimb suspension on cytosolic Ca2+ and [3H]ryanodine binding in cardiac myocytes.

Effects of a 14-day hindlimb suspension were examined on [3H]ryanodine binding to rat ventricular microsomes and on cytosolic Ca2+ concentration ([Ca2+]i) and voltage-dependent Ca2+channels in isolated ventricular myocytes. In suspended rats, the amplitude of the twitch [Ca2+]itransient was increased without significant modifications of the basal [Ca2+]iand sarcoplasmic reticulum content. Because cell capacitance, L-type Ca2+-current density, and Ca2+-channel gating were not significantly modified after suspension, the increase in [Ca2+]iwas expected to reside in a change in ryanodine receptors. Scatchard analysis of [3H]ryanodine binding revealed that suspension enhanced binding by increasing the affinity of the receptors for [3H]ryanodine without affecting the maximal binding capacity. Both Ca2+-release channel activity and [3H]ryanodine binding are modulated by Ca2+. However, the Ca2+ sensitivity of [3H]ryanodine binding remained unchanged after suspension. Taken together, these results suggest that the increase in twitch [Ca2+]itransients after suspension may result from a change in the intrinsic properties of the ryanodine receptors but not from a change in the expression level of these receptors.
A Variable Oscillator Underlies the Measurement of Time Intervals in the Rostral Medial Prefrontal Cortex during Classical Eyeblink Conditioning in Rabbits

We were interested in determining whether rostral medial prefrontal cortex (rmPFC) neurons participate in the measurement of conditioned stimulus–unconditioned stimulus (CS-US) time intervals during classical eyeblink conditioning. Rabbits were conditioned with a delay paradigm consisting of a tone as CS. The CS started 50, 250, 500, 1000, or 2000 ms before and coterminated with an air puff (100 ms) directed at the cornea as the US. Eyelid movements were recorded with the magnetic search coil technique and the EMG activity of the orbicularis oculi muscle. Firing activities of rmPFC neurons were recorded across conditioning sessions. Reflex and conditioned eyelid responses presented a dominant oscillatory frequency of ≈12 Hz. The firing rate of each recorded neuron presented a single peak of activity with a frequency dependent on the CS-US interval (i.e., ≈12 Hz for 250 ms, ≈6 Hz for 500 ms, and≈3 Hz for 1000 ms). Interestingly, rmPFC neurons presented their dominant firing peaks at three precise times evenly distributed with respect to CS start and also depending on the duration of the CS-US interval (only for intervals of 250, 500, and 1000 ms). No significant neural responses were recorded at very short (50 ms) or long (2000 ms) CS-US intervals. rmPFC neurons seem not to encode the oscillatory properties characterizing conditioned eyelid responses in rabbits, but are probably involved in the determination of CS-US intervals of an intermediate range (250–1000 ms). We propose that a variable oscillator underlies the generation of working memories in rabbits. SIGNIFICANCE STATEMENT The way in which brains generate working memories (those used for the transient processing and storage of newly acquired information) is still an intriguing question. Here, we report that the firing activities of neurons located in the rostromedial prefrontal cortex recorded in alert behaving rabbits are controlled by a dynamic oscillator. This oscillator generated firing frequencies in a variable band of 3–12 Hz depending on the conditioned stimulus–unconditioned stimulus intervals (1 s, 500 ms, 250 ms) selected for classical eyeblink conditioning of behaving rabbits. Shorter (50 ms) and longer (2 s) intervals failed to activate the oscillator and prevented the acquisition of conditioned eyelid responses. This is an unexpected mechanism to generate sustained firing activities in neural circuits generating working memories.
Role of IL-6 and TNF in thermoregulation and survival during sepsis in mice.

Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) have been implicated as key mediators in inflammation, morbidity, and mortality associated with sepsis. We examined the role of IL-6 and TNF-α signaling on hypothermia, fever, cachexia, anorexia, and survival during sepsis induced by cecal ligation and puncture (CLP) in male and female gene knockout mice. Male wild-type mice developed an initial hypothermia and subsequent fever during sepsis. Male IL-6 knockout mice did not develop fever; rather, they maintained a profound hypothermia during sepsis. Male TNF p55/p75 receptor (TNFR) knockout mice had attenuated hypothermia, but developed a virtually identical fever as wild-type mice. Cachexia did not differ between male wild-type and IL-6 or TNFR knockout mice, whereas anorexia was prolonged in IL-6 knockout mice. Due to the rapid lethality of sepsis in female mice, survival was the only variable we were able to statistically compare among female genotypes. Female wild-type mice had significantly decreased survival compared with male wild-type mice. Survival was significantly enhanced in male and female TNFR knockout mice compared with their wild-type controls. Lack of IL-6 did not affect male or female lethality. These data support the hypothesis that IL-6 is a key mediator of fever and food intake, whereas TNF is responsible for the initial hypothermia and lethality of sepsis in both sexes of mice. The enhanced lethality of CLP-treated female mice supports a role for sex steroids during sepsis.
Bananas in space: extending fold and unfold to exponential types

Fold and unfold are general purpose functionals for process-ing and constructing lists. By using the categorical approach of modelling recursive datatypes as fixed points of functors, these functionals and their algebraic properties were generalised from lists to polynomial (sum-of-product) datatypes. However, the restriction to polynomial datatypes is a serious limitation: it precludes the use of exponentials (function-spaces), whereas it is central to functional programming that functions are first-class values, and so exponentials should be able to be used freely in datatype definitions. In this paper we explain how Freyd’s work on modelling recursive datatypes as fixed points of difunctors shows how to generalise fold and unfold from polynomial datatypes to those involving exponentials. Knowledge of category theory is not required; we use Gofer throughout as our meta-language, making extensive use of constructor classes
Endothelin antagonists block α1-adrenergic constriction of coronary arterioles.

We have previously observed that intracoronary administration of the α1-adrenergic agonist phenylephrine (PE) over a period of minutes induced both an immediate and long-lasting (2 h) vasoconstriction of epicardial coronary arterioles. Because it is unlikely that α1-adrenergic constriction would persist for hours after removal of the agonist, this observation supports the view that another constrictor(s) is released during α1-adrenergic activation and induces the prolonged vasoconstriction. Therefore, we hypothesized that the prolonged microvascular constriction after PE is due to the production of endothelin (ET). We focused on ET not only because this peptide produces potent vasoconstriction but also because its vasoconstrictor action is characterized by a long duration. To test this hypothesis, the diameters of coronary arterioles (<222 μm) in the beating heart of pentobarbital-anesthetized dogs with stroboscopic intravital microscopy were measured during a 15-min intracoronary infusion of PE (1 μg ⋅ kg-1 ⋅ min-1) and at 15-min intervals for a total of 120 min. All experiments were performed in the presence of β-adrenergic blockade with propranolol. At 120 min, arterioles in the PE group were constricted (-23 ± 9% change in diameter vs. baseline). Pretreatment with the ET-converting enzyme inhibitor phosphoramidon or the ETA-receptor antagonist FR-139317 prevented the PE-induced constriction at 120 min (-1 ± 3 and -6 ± 3%, respectively, P < 0.01 vs. PE). Pretreatment with the selective α1-adrenergic antagonist prazosin (Prz) also prevented the sustained constriction (0 ± 2%, P < 0.01 vs. PE) but Prz given 60 min after PE infusion did not (-13 ± 3%). In the aggregate, these results show that vasoconstriction of epicardial coronary arterioles via α1-adrenergic activation is blocked by an ET antagonist and an inhibitor of its production. From these data, we conclude that α1-adrenergic activation promotes the production and/or release of ET, which produces or facilitates microvascular constriction of epicardial canine coronary arterioles.
VISA: visual subspace clustering analysis

To gain insight into today's large data resources, data mining extracts interesting patterns. To generate knowledge from patterns and benefit from human cognitive abilities, meaningful visualization of patterns are crucial. Clustering is a data mining technique that aims at grouping data to patterns based on mutual (dis)similarity. For high dimensional data, subspace clustering searches patterns in any subspace of the attributes as patterns are typically obscured by many irrelevant attributes in the full space. For visual analysis of subspace clusters, their comparability has to be ensured. Existing subspace clustering approaches, however, lack interactive visualization and show bias with respect to the dimensionality of subspaces. In this work, dimensionality unbiased subspace clustering and a novel distance function for subspace clusters are proposed. We suggest two visualization techniques that allow users to browse the entire subspace clustering, to zoom into individual objects, and to analyze subspace cluster characteristics in-depth. Bracketing of different parameter settings enable users to immediately see the effect of parameters on their data and hence to choose the best clustering result for further analysis. Usage of user analysis for feedback to the subspace clustering algorithm directly improves the subspace clustering. We demonstrate our visualization techniques on real world data and confirm results through additional accuracy measurements and comparison with existing subspace clustering algorithms.
Targeting DTL induces cell cycle arrest and senescence and suppresses cell growth and colony formation through TPX2 inhibition in human hepatocellular carcinoma cells

Background Hepatocellular carcinoma (HCC) has an increasing incidence and high mortality. Surgical operation is not a comprehensive strategy for liver cancer. Moreover, tolerating systemic chemotherapy is difficult for patients with HCC because hepatic function is often impaired due to underlying cirrhosis. Therefore, a comprehensive strategy for cancer treatment should be developed. DTL (Cdc10-dependent transcript 2) is a critical regulator of cell cycle progression and genomic stability. In our previous study, the upregulation of DTL expression in aggressive HCC correlated positively with tumor grade and poor patient survival. We hypothesize that targeting DTL may provide a novel therapeutic strategy for liver cancer. DTL small interference RNAs were used to knock down DTL protein expression. Methods A clonogenic assay, immunostaining, double thymidine block, imaging flow cytometry analysis, and a tumor spheroid formation assay were used to analyze the role of DTL in tumor cell growth, cell cycle progression, micronucleation, ploidy, and tumorigenicity. Results Our results demonstrated that targeting DTL reduced cell cycle regulators and chromosome segregation genes, resulting in increased cell micronucleation. DTL depletion inhibited liver cancer cell growth, increased senescence, and reduced tumorigenesis. DTL depletion resulted in the disruption of the mitotic proteins cyclin B, CDK1, securin, seprase, Aurora A, and Aurora B as well as the upregulation of the cell cycle arrest gene p21. A rescue assay indicated that DTL should be targeted through TPX2 downregulation for cancer cell growth inhibition. Moreover, DTL silencing inhibited the growth of patient-derived primary cultured HCC cells. Conclusion Our study results indicate that DTL is a potential novel target gene for treating liver cancer through liver cancer cell senescence induction. Furthermore, our results provide insights into molecular mechanisms for targeting DTL in liver cancer cells. The results also indicate several other starting points for future preclinical and clinical studies on liver cancer treatment.
Osteocyte hypoxia: a novel mechanotransduction pathway.

Bone is a unique tissue in which to examine mechanotransduction due to its essential role in weight bearing. Within bone, the osteocyte is an ideal cellular mechanotransducer candidate. Because osteocytes reside distant from the blood supply, their metabolic needs are met by a combination of passive diffusion and enhanced diffusion, arising when the tissue is loaded during functional activity. Therefore, we hypothesized that depriving a bone of mechanical loading (and thus eliminating diffusion enhanced by loading) would rapidly induce osteocyte hypoxia. Using the avian ulna model of disuse osteopenia, we found that 24 h of unloading results in significant osteocyte hypoxia (8.4 ± 1.8%) compared with control levels (1.1 ± 0.5%; P = 0.03). Additionally, we present preliminary data suggesting that a brief loading regimen is sufficient to rescue osteocytes from this fate. The rapid onset of the observed osteocyte hypoxia, the inhibition of hypoxia by brief loading, and the cellular consequences of oxygen deprivation are suggestive of a novel mechanotransduction pathway with implications across organ systems.
Robotics-inspired biology

ABSTRACT For centuries, designers and engineers have looked to biology for inspiration. Biologically inspired robots are just one example of the application of knowledge of the natural world to engineering problems. However, recent work by biologists and interdisciplinary teams have flipped this approach, using robots and physical models to set the course for experiments on biological systems and to generate new hypotheses for biological research. We call this approach robotics-inspired biology; it involves performing experiments on robotic systems aimed at the discovery of new biological phenomena or generation of new hypotheses about how organisms function that can then be tested on living organisms. This new and exciting direction has emerged from the extensive use of physical models by biologists and is already making significant advances in the areas of biomechanics, locomotion, neuromechanics and sensorimotor control. Here, we provide an introduction and overview of robotics-inspired biology, describe two case studies and suggest several directions for the future of this exciting new research area. Summary: Robotic devices are increasingly generating ideas for experiments on living animals, a new twist on the inspiration that biologists have traditionally taken from mechanical systems.
Identification of Leaf Promoters for Use in Transgenic Wheat

Wheat yields have plateaued in recent years and given the growing global population there is a pressing need to develop higher yielding varieties to meet future demand. Genetic manipulation of photosynthesis in elite wheat varieties offers the opportunity to significantly increase yields. However, the absence of a well-defined molecular tool-box of promoters to manipulate leaf processes in wheat hinders advancements in this area. Two promoters, one driving the expression of sedoheptulose-1,7-bisphosphatase (SBPase) and the other fructose-1,6-bisphosphate aldolase (FBPA) from Brachypodium distachyon were identified and cloned into a vector in front of the GUS reporter gene. Both promoters were shown to be functionally active in wheat in both transient assays and in stably transformed wheat plants. Analysis of the stable transformants of wheat (cv. Cadenza) showed that both promoters controlled gus expression throughout leaf development as well as in other green tissues. The availability of these promoters provides new tools for the expression of genes in transgenic wheat leaves and also paves the way for multigene manipulation of photosynthesis to improve yields.
NO from smooth muscle cells decreases NOS expression in endothelial cells: role of TNF-α.

Despite the evidence that cytokines stimulate nitric oxide (NO) production by inducible nitric oxide synthase (iNOS), several reports recently demonstrated that the hypotensive response related to endothelial nitric oxide synthase (eNOS) activity could be inhibited by the same cytokines. The aim of the present work was to analyze whether NO generated by vascular smooth muscle cells (VSMC) could modify eNOS protein expression in endothelial cells. Bovine aortic endothelial cells (BAEC) and bovine VSMC (BVSMC) in coculture were used for the study. Interleukin-1β (IL-1β, 10 ng/ml)-treated BVSMC, which expressed iNOS protein, decreased eNOS protein expression in BAEC. The presence of NO antagonists N ω-nitro-l-arginine methyl ester (10-3 mol/l) or N G-monomethyl-l-arginine (10-3 mol/l) prevented the decrease in eNOS protein expression induced by IL-1β-treated BVSMC. Surprisingly, two different NO donors, 3-morpholinosydnonimine (10-4 mol/l) and S-nitroso- N-acetyl-d,l-penicillamine (10-4 mol/l), failed to modify eNOS expression in BAEC, suggesting the existence of a diffusible mediator released from IL-1β-treated BVSMC that acts on endothelial cells by reducing eNOS expression. The presence of NO antagonists reduced tumor necrosis factor-α (TNF-α) production by IL-1β-stimulated BVSMC. This effect was also produced in the presence of a protein kinase G inhibitor, guanosine-5'-O-(2-thiodiphosphate) trilithium salt. A polyclonal antibody against TNF-α prevented eNOS expression in the BAEC-BVSMC coculture. In conclusion, NO by itself failed to modify eNOS protein expression in endothelial cells but increased TNF-α generation by IL-1β-stimulated BVSMC and, in this way, reduced eNOS expression in the endothelium.
Electrospun Fibrous Scaffolds for Small-Diameter Blood Vessels: A Review

Small-diameter blood vessels (SDBVs) are still a challenging task to prepare due to the occurrence of thrombosis formation, intimal hyperplasia, and aneurysmal dilation. Electrospinning technique, as a promising tissue engineering approach, can fabricate polymer fibrous scaffolds that satisfy requirements on the construction of extracellular matrix (ECM) of native blood vessel and promote the adhesion, proliferation, and growth of cells. In this review, we summarize the polymers that are deployed for the fabrication of SDBVs and classify them into three categories, synthetic polymers, natural polymers, and hybrid polymers. Furthermore, the biomechanical properties and the biological activities of the electrospun SBVs including anti-thrombogenic ability and cell response are discussed. Polymer blends seem to be a strategic way to fabricate SDBVs because it combines both suitable biomechanical properties coming from synthetic polymers and favorable sites to cell attachment coming from natural polymers.
Based on GPRS

Internet technology has emerged as the major driving force behind new developments in the area of telecommunications networks. The volume of packet data traffic has increased at extreme rates. In order to meet these changing traffic patterns, more and more network operators adapt their strategies and plan to migrate to IP-based backbone networks. Clearly, the Internet will dominate our daily life in the future much more than today. Meanwhile, mobile networks face a similar trend of exponential traffic increase and growing importance to users. In some countries, such as Finland, the number of mobile subscriptions has recently exceeded the number of fixed lines. This tremendous success was not expected in the 1980s, when today's second-generation mobile communication systems were designed. The combination of both developments, the growth of the Internet and the success of mobile networks, suggests that the next trend will be an increasing demand for mobile access to Internet applications. It is therefore increasingly important that mobile radio networks support these applications in an efficient manner. Thus, mobile radio systems currently under development include support for packet data services. The most widely deployed standard for second-generation mobile radio networks is the Global System for Mobile Communications (GSM) [1]. Networks based on this standard will be extended in the near future with the General Packet Radio Service (GPRS), which provides data rates up to 160 kb/s. When discussions about GPRS started in the early 1990s, applications such as road transport telematics and financial services were driving the demand. The high costs for circuit-switched GSM connections prevented the widespread use of mobile data transmission for such services. In recent years, however, end-user applications such as Web browsing and e-mail are becoming increasingly popular; therefore, the Inter-net has dominated the standardization of GPRS. Internet applications are predicted to contribute the largest share of the expected traffic volume. In brief, GPRS can be described as a service providing optimized access to the Internet, while reusing to a large degree existing GSM infrastructure. Advanced mobile terminals using multiple slots will offer more convenient and faster Internet access than today's technology. The GPRS concept allows volume-oriented charging, which permits users to have cheap, permanent connections to the Internet. This article concentrates on two objectives. First, it provides an overview of GPRS, including technology, architecture , and applicability; second, it presents some simulation results that exhibit the GPRS performance. In particular, the article analyzes Web …