A novel method to identify cooperative functional modules: study of module coordination in the Saccharomyces cerevisiae cell cycle

<p>Abstract</p> <p>Background</p> <p>Identifying key components in biological processes and their associations is critical for deciphering cellular functions. Recently, numerous gene expression and molecular interaction experiments have been reported in <it>Saccharomyces cerevisiae</it>, and these have enabled systematic studies. Although a number of approaches have been used to predict gene functions and interactions, tools that analyze the essential coordination of functional components in cellular processes still need to be developed.</p> <p>Results</p> <p>In this work, we present a new approach to study the cooperation of functional modules (sets of functionally related genes) in a specific cellular process. A cooperative module pair is defined as two modules that significantly cooperate with certain functional genes in a cellular process. This method identifies cooperative module pairs that significantly influence a cellular process and the correlated genes and interactions that are essential to that process. Using the yeast cell cycle as an example, we identified 101 cooperative module associations among 82 modules, and importantly, we established a cell cycle-specific cooperative module network. Most of the identified module pairs cover cooperative pathways and components essential to the cell cycle. We found that 14, 36, 18, 15, and 20 cooperative module pairs significantly cooperate with genes regulated in early G1, late G1, S, G2, and M phase, respectively. Fifty-nine module pairs that correlate with Cdc28 and other essential regulators were also identified. These results are consistent with previous studies and demonstrate that our methodology is effective for studying cooperative mechanisms in the cell cycle.</p> <p>Conclusions</p> <p>In this work, we propose a new approach to identifying condition-related cooperative interactions, and importantly, we establish a cell cycle-specific cooperation module network. These results provide a global view of the cell cycle and the method can be used to discover the dynamic coordination properties of functional components in other cellular processes.</p

Bifurcation and hysteresis of flow pattern transition in a shallow molten silicon pool with Cz configuration

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Computational modeling with forward and reverse engineering links signaling network and genomic regulatory responses: NF-κB signaling-induced gene expression responses in inflammation

<p>Abstract</p> <p>Background</p> <p>Signal transduction is the major mechanism through which cells transmit external stimuli to evoke intracellular biochemical responses. Diverse cellular stimuli create a wide variety of transcription factor activities through signal transduction pathways, resulting in different gene expression patterns. Understanding the relationship between external stimuli and the corresponding cellular responses, as well as the subsequent effects on downstream genes, is a major challenge in systems biology. Thus, a systematic approach is needed to integrate experimental data and theoretical hypotheses to identify the physiological consequences of environmental stimuli.</p> <p>Results</p> <p>We proposed a systematic approach that combines forward and reverse engineering to link the signal transduction cascade with the gene responses. To demonstrate the feasibility of our strategy, we focused on linking the NF-κB signaling pathway with the inflammatory gene regulatory responses because NF-κB has long been recognized to play a crucial role in inflammation. We first utilized forward engineering (Hybrid Functional Petri Nets) to construct the NF-κB signaling pathway and reverse engineering (Network Components Analysis) to build a gene regulatory network (GRN). Then, we demonstrated that the corresponding IKK profiles can be identified in the GRN and are consistent with the experimental validation of the IKK kinase assay. We found that the time-lapse gene expression of several cytokines and chemokines (TNF-α, IL-1, IL-6, CXCL1, CXCL2 and CCL3) is concordant with the NF-κB activity profile, and these genes have stronger influence strength within the GRN. Such regulatory effects have highlighted the crucial roles of NF-κB signaling in the acute inflammatory response and enhance our understanding of the systemic inflammatory response syndrome.</p> <p>Conclusion</p> <p>We successfully identified and distinguished the corresponding signaling profiles among three microarray datasets with different stimuli strengths. In our model, the crucial genes of the NF-κB regulatory network were also identified to reflect the biological consequences of inflammation. With the experimental validation, our strategy is thus an effective solution to decipher cross-talk effects when attempting to integrate new kinetic parameters from other signal transduction pathways. The strategy also provides new insight for systems biology modeling to link any signal transduction pathways with the responses of downstream genes of interest.</p

Enhanced photo-excitation and angular-momentum imprint of gray excitons in WSe2_{2} monolayers by spin-orbit-coupled vector vortex beams

A light beam can be spatially structured in the complex amplitude to possess orbital angular momentum (OAM), which introduces a new degree of freedom alongside the intrinsic spin angular momentum (SAM) associated with circular polarization. Moreover, super-imposing two twisted lights with distinct SAM and OAM produces a vector vortex beam (VVB) in non-separable states where not only complex amplitude but also polarization are spatially structured and entangled with each other. In addition to the non-separability, the SAM and OAM in a VVB are intrinsically coupled by the optical spin-orbit interaction and constitute the profound spin-orbit physics in photonics. In this work, we present a comprehensive theoretical investigation, implemented on the first-principles base, of the intriguing light-matter interaction between VVBs and WSe$_{2}$ monolayers (WSe$_{2}$-MLs), one of the best-known and promising two-dimensional (2D) materials in optoelectronics dictated by excitons, encompassing bright exciton (BX) as well as various dark excitons (DXs). One of the key findings of our study is the substantial enhancement of the photo-excitation of gray excitons (GXs), a type of spin-forbidden dark exciton, in a WSe$_2$-ML through the utilization of a twisted light that possesses a longitudinal field associated with the optical spin-orbit interaction. Our research demonstrates that a spin-orbit-coupled VVB surprisingly allows for the imprinting of the carried optical information onto gray excitons in 2D materials, which is robust against the decoherence mechanisms in materials. This observation suggests a promising method for deciphering the transferred angular momentum from structured lights to excitons

Differential effects of neurotrophins and schwann cell-derived signals on neuronal survival/growth and synaptogenesis

Recent studies have shown that the survival of mammalian motoneurons in vitro is promoted by neurotrophins (NTs) and cAMP. There is also evidence that neurotrophins enhance transmitter release.Wethus investigated whether these agents also promote synaptogenesis. Cultured Xenopus spinal cord neurons were treated with a mixture of BDNF, glia-derived neurotrophic factor, NT-3, and NT-4, in addition to forskolin and IBMX or the cell-permeant form of cAMP, to elevate the cAMP level. The outgrowth and survival of neurons were dramatically increased by this trophic stimulation. However, when these neurons were cocultured with muscle cells, the trophic agents resulted in a failure of synaptogenesis. Specifically, the induction ofAChreceptor (AChR) clustering in cultured muscle cells was inhibited at nerve–muscle contacts, in sharp contrast to control, untreated cocultures. Because AChR clustering induced by agrin or growth factor-coated beads in muscle cells was unaffected by trophic stimulation, its effect on synaptogenesis is presynaptic in origin. In the control, agrin was deposited along the neurite and at nerve–muscle contacts. This was significantly downregulated in cultures treated with trophic stimuli. Reverse transcriptase-PCR analyses showed that this decrease in agrin deposition was caused by an inhibition of agrin synthesis by trophic stimuli. Both agrin synthesis and induction of AChR clustering were restored under trophic stimulation when Schwann cell-conditioned medium was introduced. These results suggest that trophic stimulation maintains spinal neurons in the growth state, and Schwann cell-derived factors allow them to switch to the synaptogenic state

Renal Protection for Coronary Angiography in Advanced Renal Failure Patients by Prophylactic Hemodialysis A Randomized Controlled Trial

ObjectivesWe performed a study to determine whether prophylactic hemodialysis reduces contrast nephropathy (CN) after coronary angiography in advanced renal failure patients.BackgroundPre-existing renal failure is the greatest risk factor for CN. Hemodialysis can effectively remove contrast media, but its effect upon preventing CN is still uncertain.MethodsEighty-two patients with chronic renal failure, referred for coronary angiography, were assigned randomly to receive either normal saline intravenously and prophylactic hemodialysis (dialysis group; n = 42) or fluid supplement only (control group; n = 40).ResultsProphylactic hemodialysis lessened the decrease in creatinine clearance within 72 h in the dialysis group (0.4 ± 0.9 ml/min/1.73 m2vs. 2.2 ± 2.8 ml/min/1.73 m2; p < 0.001). Compared with the dialysis group, the serum creatinine concentrations in the control group were significantly higher at day 4 (6.3 ± 2.3 mg/dl vs. 5.1 ± 1.3 mg/dl; p = 0.010) and at peak level (6.7 ± 2.7 mg/dl vs. 5.3 ± 1.5 mg/dl; p = 0.005). Temporary renal replacement therapy was required in 35% of the control patients and in 2% of the dialysis group (p < 0.001). Thirteen percent of the control patients, but none of the dialysis patients, required long-term dialysis after discharge (p = 0.018). For the patients not requiring chronic dialysis, 13 patients in the control group (37%) and 2 in the dialysis group (5%) had an increase in serum creatinine concentration at discharge of more than 1 mg/dl from baseline (p < 0.001).ConclusionsProphylactic hemodialysis is effective in improving renal outcome in chronic renal failure patients undergoing coronary angiography

Fak56 functions downstream of integrin alphaPS3betanu and suppresses MAPK activation in neuromuscular junction growth

Background: Focal adhesion kinase (FAK) functions in cell migration and signaling through activation of the mitogen-activated protein kinase (MAPK) signaling cascade. Neuronal function of FAK has been suggested to control axonal branching; however, the underlying mechanism in this process is not clear. Results: We have generated mutants for the Drosophila FAK gene, Fak56. Null Fak56 mutants display overgrowth of larval neuromuscular junctions (NMJs). Localization of phospho-FAK and rescue experiments suggest that Fak56 is required in presynapses to restrict NMJ growth. Genetic analyses imply that FAK mediates the signaling pathway of the integrin αPS3βν heterodimer and functions redundantly with Src. At NMJs, Fak56 downregulates ERK activity, as shown by diphospho-ERK accumulation in Fak56 mutants, and suppression of Fak56 mutant NMJ phenotypes by reducing ERK activity. Conclusion: We conclude that Fak56 is required to restrict NMJ growth during NMJ development. Fak56 mediates an extracellular signal through the integrin receptor. Unlike its conventional role in activating MAPK/ERK, Fak56 suppresses ERK activation in this process. These results suggest that Fak56 mediates a specific neuronal signaling pathway distinct from that in other cellular processes