Systems‐biology can identify novel drug targets through computational analysis of cellular regulatory networks, and nanomaterial engineering can develop nanocarriers to deliver therapeutic agents to ...the specific target of cancer cells. In article number 1906783, Kwang‐Hyun Cho and co‐workers review the recent progress and challenges in systems biology and nanomedicine and their integration with a view toward cancer precision medicine.
The estimated glomerular filtration rate (eGFR) at 6 months after donation (eGFR
) is strongly associated with the risk of end-stage renal disease in living kidney donors. This study aimed to ...investigate the incidence of eGFR
<60 mL/min/1.73 m² (eGFR
<60) and identify the risk factors that can predict the occurrence of eGFR
<60 in living kidney donors.
Living kidney donors who underwent nephrectomy at Severance Hospital between January 2009 and December 2019 were identified. We excluded 94 of 1233 donors whose creatinine values at 6 months after donation were missing. The risk factors for eGFR
<60 were assessed using multivariate regression analysis. The optimal cutoff points for candidate risk factors for predicting eGFR
<60 occurrence were determined using the Youden index.
The eGFR
<60 occurred in 17.3% of the participants. Older age (≥44 years), history of hypertension, lower preoperative eGFR (<101 mL/min/1.73 m²), and degree of increase in creatinine levels on postoperative day 2 compared to those before surgery (ΔCr2_pre) (≥0.39 mg/dL) increased the risk of eGFR
<60. The addition of ΔCr2_pre to preoperative eGFR yielded a higher predictive accuracy for predicting eGFR
<60 than that with preoperative eGFR alone {area under the receiver operating characteristic curve=0.886 95% confidence interval (CI), 0.863-0.908 vs. 0.862 (95% CI, 0.838-0.887),
<0.001}.
The incidence of eGFR
<60 was 17.3%. Older age, lower preoperative eGFR, history of hypertension, and greater ΔCr2_pre were associated with the occurrence of eGFR
<60 after living donor nephrectomy. The combination of preoperative eGFR and ΔCr2_pre showed the highest predictive power for eGFR
<60.
The brain requires task-dependent interregional coherence of information flow in the anatomically connected neural network. However, it is still unclear how a neuronal group can flexibly select its ...communication target. In this study, we revealed a hidden routing mechanism on the basis of recurrent connections. Our simulation results based on the spike response model show that recurrent connections between excitatory and inhibitory neurons modulate the resonant frequency of a local neuronal group, and that this modulation enables a neuronal group to receive selective information by filtering a preferred frequency component. We also found that the recurrent connection facilitates the successful routing of any necessary information flow between neuronal groups through frequency-dependent resonance of synchronized oscillations. Taken together, these results suggest that recurrent connections act as a phase-locking neuronal tuner which determines the resonant frequency of a local group and thereby controls the preferential routing of incoming signals.
Adrenal insufficiency (AI) is associated with high morbidity and mortality. The aim of this systematic review was to enhance diagnostic approaches and summarize therapeutic strategies in the ...management of AI in patients with systematic lupus erythematosus (SLE) or antiphospholipid syndrome (APS).
A literature search of PubMed and Medline databases was performed and 91 publications containing 105 cases were included for the final analysis.
The following frequency of clinical signs and symptoms was noted: abdominal pain (39.04%) was the leading symptom, followed by fever (33.33%), vomiting (23.81%), and nausea (19.05%). APS was present in 73%, SLE in 17% of the patients, while 2% had a diagnosis of both, SLE and APS. ACTH stimulation test (ACTHst) was performed in 18% of cases and 76.6% of them were unresponsive towards stimulation. Variable treatment approaches were used: hydrocortisone was most commonly used (38.09%), followed by fludrocortisone (26.67%), prednisolone (20.00%) and volume replacement treatment (11.43%), respectively.
This analysis highlights the importance of an early diagnosis and initiation of therapeutic management when AI is suspected. In line, signs and symptoms related to autoimmune diseases in patients with AI should be reviewed crtitically.
Biological oscillations are found ubiquitously in cells and are widely variable, with periods varying from milliseconds to months, and scales involving subcellular components to large groups of ...organisms. Interestingly, independent oscillators from different cells often show synchronization that is not the consequence of an external regulator. What is the underlying design principle of such synchronized oscillations, and can modeling show that the complex consequences arise from simple molecular or other interactions between oscillators? When biological oscillators are coupled with each other, we found that synchronization is induced when they are connected together through a positive feedback loop. Increasing the coupling strength of two independent oscillators shows a threshold beyond which synchronization occurs within a few cycles, and a second threshold where oscillation stops. The positive feedback loop can be composed of either double-positive (PP) or double-negative (NN) interactions between a node of each of the two oscillating networks. The different coupling structures have contrasting characteristics. In particular, PP coupling is advantageous with respect to stability of period and amplitude, when local oscillators are coupled with a short time delay, whereas NN coupling is advantageous for a long time delay. In addition, PP coupling results in more robust synchronized oscillations with respect to amplitude excursions but not period, with applied noise disturbances compared to NN coupling. However, PP coupling can induce a large fluctuation in the amplitude and period of the resulting synchronized oscillation depending on the coupling strength, whereas NN coupling ensures almost constant amplitude and period irrespective of the coupling strength. Intriguingly, we have also observed that artificial evolution of random digital oscillator circuits also follows this design principle. We conclude that a different coupling strategy might have been selected according to different evolutionary requirements.
To present normative data of optical coherence tomography (OCT) parameters, electrophysiological tests, and optical biometry conducted for cynomolgus monkeys.
Multimodal examinations were performed ...for 11 adult cynomolgus monkeys (Macaca fascicularis, weighing 2.6-7.5 kg, aged 45-99 months). A-scan biometry was performed to measure ocular biometry. OCT images were obtained at 30° and 55°. After the pupils were fully dilated, electroretinogram (ERG) and visual evoked potentials (VEP) were recorded with a commercial system using a contact lens electrode.
All cynomolgus monkeys were males. The mean axial length was 17.92 ± 0.34 mm. The central total retinal layer (TRL) and subfoveal choroidal thicknesses were 286.27 ± 18.43 and 234.73 ± 53.93 µm, respectively. The TRL and nerve fiber layer thickness was greater in the nasal than in other quadrants in the Early Treatment Diabetic Retinopathy Study circle in the macula. Peripheral TRL and ganglion cell complex thickness on the temporal outside the vascular arcades were lower than on the other sides. The peak latency of a-wave and b-wave in scotopic and photopic 3.0 ERG was 14.78 ± 1.00 and 32.89 ± 1.81 ms, and 12.91 ± 1.03 and 31.79 ± 2.16 ms, respectively. The n2 wave peak latency of VEP was 15.21 ± 8.07 ms. The a-wave peak latency of ERG and the n2 wave peak latency of VEP negatively correlated with age.
The normative ocular biometric, electrophysiological test, and OCT parametric data of cynomolgus monkeys could serve as reference values for further preclinical studies.
We present normative data of cynomolgus monkeys' eyes, an adequate animal model for preclinical studies.
The reverse control of irreversible biological processes Cho, Kwang‐Hyun; Joo, Jae Il; Shin, Dongkwan ...
Wiley interdisciplinary reviews. Systems biology and medicine,
September/October 2016, Letnik:
8, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Most biological processes have been considered to be irreversible for a long time, but some recent studies have shown the possibility of their reversion at a cellular level. How can we then ...understand the reversion of such biological processes? We introduce a unified conceptual framework based on the attractor landscape, a molecular phase portrait describing the dynamics of a molecular regulatory network, and the phenotype landscape, a map of phenotypes determined by the steady states of particular output molecules in the attractor landscape. In this framework, irreversible processes involve reshaping of the phenotype landscape, and the landscape reshaping causes the irreversibility of processes. We suggest reverse control by network rewiring which changes network dynamics with constant perturbation, resulting in the restoration of the original phenotype landscape. The proposed framework provides a conceptual basis for the reverse control of irreversible biological processes through network rewiring. WIREs Syst Biol Med 2016, 8:366–377. doi: 10.1002/wsbm.1346
This article is categorized under:
Biological Mechanisms > Regulatory Biology
► Small-world network during working memory was investigated using the EEG. ► Small-worldness is reduced in first-episode schizophrenia and intermediate in UHR. ► Suboptimal network integration is ...suggested in schizophrenia pathophysiology.
Disturbances of functional interaction between different brain regions have been hypothesized to be the major pathophysiological mechanism underlying the cognitive deficits of schizophrenia. We investigated the small-world functional networks in individuals at ultra-high risk (UHR) for psychosis, first-episode schizophrenia (FESPR) patients, and healthy controls. All participants underwent the electroencephalogram during a control task and a working memory (WM) task. Small-world properties of the theta band were reduced in FESPR relative to controls during the WM task. Small-worldness of the UHR during the WM task exhibited intermediate value between that of controls and FESPR. These results imply that the suboptimal organization of the brain network may play a pivotal role in the schizophrenia pathophysiology.
Prostaglandin E2 (PGE2) is known to have a key role in the development of colorectal cancer, but previous experiments showed its contrasting (i.e. tumor-promoting or tumor-suppressive) roles ...depending on experimental conditions. To elucidate the mechanisms underlying such contrasting roles of PGE2 in tumorigenesis, we investigated all the previous experiments and found a new signal transduction pathway mediated by retinoic acid receptor-related orphan receptor (ROR)α, in which PGE2/PKCα-dependent phosphorylation of RORα attenuates Wnt target gene expression in colon cancer cells. From mathematical simulations combined with biochemical experimentation, we revealed that RORα induces a biphasic response of Wnt target genes to PGE2 stimulation through a regulatory switch formed by an incoherent feedforward loop, which provides a mechanistic explanation on the contrasting roles of PGE2 observed in previous experiments. More interestingly, we found that RORα constitutes another regulatory switch formed by coupled positive and negative feedback loops, which regulates the hysteretic response of Wnt signaling and eventually converts a proliferative cellular state into an anti-proliferative state in a very delicate way. Our results indicate that RORα is the key regulator at the center of these hidden switches that critically regulate cancer cell proliferation and thereby being a promising anti-cancer therapeutic target.
Electron transport in the Aharonov-Bohm pump SHIN, Dongkwan; HONG, Jongbae
Physical review. B, Condensed matter and materials physics,
08/2004, Letnik:
70, Številka:
7
Journal Article
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