Mystery at the heart of life

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December 21, 2014

Cell biology, Intelligent Design, News

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Cell biology
Intelligent Design
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By Biologic Institute’s Ann Gauger, at Christianity Today’s Behemoth, the secret life of cells:

Our bodies are made up of some 100 trillion cells. We tend to think of cells as static, because that’s how they were presented to us in textbooks. In fact, the cell is like the most antic, madcap, crowded (yet fantastically efficient) city you can picture. And at its heart lies a mystery—or I should say, several mysteries—involving three special kinds of molecules: DNA, RNA, and proteins.

These molecules are assembled into long chains called polymers, and are uniquely suited for the roles they play. More importantly, life absolutely depends upon them. We have to have DNA, RNA, and protein all present and active at the same time for a living organism to live.

How they work together so optimally and efficiently is not merely amazing, but also a great enigma, a mystery that lies at the heart of life itself. More. Paywall soon after. May be worth it.

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Comments

The emergence, over developmental time, of the pattern and form of the embryo from the fertilized egg is a topic that has engaged the interest of biologists from the earliest days of modern embryology [...] It is evident that this process involves both growth and pattern formation, but the functional relationship between these processes is as yet unclear. Ultimately, we need to understand how cells use gene products to work together to create an embryo, or to regenerate a leg, in order to track backwards to understand the role that specific molecules and genes play in enabling the relevant cellular behaviors.
The relationship between growth and pattern formation. Bryant SV, Gardiner DM Regeneration (Oxf). 3(2):103-22. doi: 10.1002/reg2.55.

Complex complexityDionisio_{December 1, 2016
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Successful development depends on the creation of spatial gradients of transcription factors within developing fields, and images of graded distributions of gene products populate the pages of developmental biology journals. Therefore the challenge is to understand how the graded levels of intracellular transcription factors are generated across fields of cells. The model of cell cycle gated transcriptional regulation brings focus back to the functional role of morphogens as cell cycle regulators, and proposes a specific and testable mechanism by which morphogens, in their roles as growth factors (how they were originally discovered), also determine cell fate.
The relationship between growth and pattern formation. Bryant SV, Gardiner DM Regeneration (Oxf). 3(2):103-22. doi: 10.1002/reg2.55.

Complex complexityDionisio_{December 1, 2016
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Mathematics is often used to model biological systems. The precise characterization of these phenomena will require a more careful analysis of the kinetics of ductal morphogenesis. In its current state, our model has some limitations. The first is that the current model only allows for changes in histology (cellular number and arrangements) not gross morphology (increased branching). A second limitation is that the parameters were evaluated as averages and assumed to be constant over time, while variations in these values could change the predicted elongation rate and may account for the natural variation in growth rates.
A Geometrically-Constrained Mathematical Model of Mammary Gland Ductal Elongation Reveals Novel Cellular Dynamics within the Terminal End Bud. Paine I1,2, Chauviere A3, Landua J1, Sreekumar A2, Cristini V4,5,6,7, Rosen J2, Lewis MT PLoS Comput Biol. 12(4):e1004839. doi: 10.1371/journal.pcbi.1004839.

Complex complexity affects the accuracy of models applied to biology.Dionisio_{December 1, 2016
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E26 transformation-specific (Ets) family of transcription factors are characterized by the presence of Ets-DNA binding domain and have been found to be highly involved in hematopoiesis and various tissue differentiation. With improved proteomics and gene editing tools that are now available, therefore, future studies which elucidate the role of ESE-1 during embryonic development will provide not only better insights into ESE-1 function in specific cell differentiation pathways, but also its interactions with other Ets family members. In addition, understanding how epithelium-specific Ets factors contribute to normal embryonic development by, for example, global gene expression analysis in systemic knockdown study (Atabakhsh et al., 2012), will help us to better understand how they take part in disorders and abnormalities which share signaling pathways and gene clusters involved in embryogenesis, such as cancer. This may open new opportunities to tackle aberrant cell differentiation or repair mechanisms that pose barriers to effective treatment, while building on our current body of knowledge on how multi-member protein families function collectively.
ESE-1 in Early Development: Approaches for the Future. Lee CM, Wu J, Xia Y, Hu J Front Cell Dev Biol. 4:73. doi: 10.3389/fcell.2016.00073.

Complex complexityDionisio_{November 30, 2016
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Sortilin has been shown to bind multiple ligands, and to have physiological functions beyond the nervous system. Possible roles for sortilin in the development of the embryo have not been examined. Whether this is due to redundancy of sortilin in thyroid gland function, or a question of experimental circumstances remain to be discovered. It is our hope that this structural characterization will encourage new studies of the functions of sortilin and SorCS2 in organ development.
Spatiotemporal patterns of sortilin and SorCS2 localization during organ development. Boggild S, Molgaard S, Glerup S, Nyengaard JR BMC Cell Biol. 17:8. doi: 10.1186/s12860-016-0085-9.

Complex complexity.Dionisio_{November 30, 2016
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Importantly, the transcriptional programs regulating the expression of specific GSL glycosyltransferases, their physical interactions and sub-Golgi compartmentalization, as well as the accessibility to their substrates are parameters that we still have not completely unravelled. […] we have little clue of how GSL synthesis is controlled. Future studies focused on the regulation of GSL metabolism, should provide a more systematic view on the GSL role in signalling and organism pathophysiology. […] a comprehensive picture of the impact of GSL composition on cell signalling and transcriptional regulation is lacking. […] only a modest number of GSLs have been studied in any real detail, thus leaving the understanding of the specific roles of most GSLs in driving differentiation processes to future research.
Glycosphingolipid–Protein Interaction in Signal Transduction Domenico Russo, Seetharaman Parashuraman and Giovanni D’Angelo Int J Mol Sci. 17(10): 1732. doi: 10.3390/ijms17101732

Complex complexity.Dionisio_{November 30, 2016
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[…] there are still many aspects to be clarified regarding how protein binding specificity is conferred by parameters such as the length of the acyl chains of the ceramide, the degree of unsaturation and how these features can specifically modulate signal transduction. The combination of all these parameters yields a further level of complexity, which constitute an additional information reservoir being perceived by direct protein interactors, and involved in the GSL-dependent fine tuning of cell signalling.
Glycosphingolipid–Protein Interaction in Signal Transduction Domenico Russo, Seetharaman Parashuraman and Giovanni D’Angelo Int J Mol Sci. 17(10): 1732. doi: 10.3390/ijms17101732

Complex complexity.Dionisio_{November 30, 2016
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[…] the extent of GSL involvement in cell regulation is not yet fully addressed. […] more effort is required to systematically identify new GSDs in the whole proteome, and to learn about their biochemical features. […] to date it is unknown how many GSD types exist, and how they are structured. […] further bioinformatics and biochemical studies are required to understand the role of GSL-glycan moieties in GSL–protein interactions. […] structural and dynamics data on GSD/GSL complexes are required to understand how each sugar residue interfaces with the surrounding amino acid counterpart. […] it will be possible in a near future to systematically reveal GSL–protein interactions.
Glycosphingolipid–Protein Interaction in Signal Transduction Domenico Russo, Seetharaman Parashuraman and Giovanni D’Angelo Int J Mol Sci. 17(10): 1732. doi: 10.3390/ijms17101732

Complex complexity.Dionisio_{November 30, 2016
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[...] although GSDs have been recognized to bind GSL-glycan portions with different affinities, the basic principles accounting for specificity of these interactions are still far from being understood. As a consequence, future developments in the field will probably derive from solving the following issues. To date, the rules determining how the information contained in GSL “words” is read are not understood. [...] we lack an estimation of the fraction of the proteome that interacts with specific GSLs and of protein domains/motifs involved in these interactions.
Glycosphingolipid–Protein Interaction in Signal Transduction Domenico Russo, Seetharaman Parashuraman and Giovanni D’Angelo Int J Mol Sci. 17(10): 1732. doi: 10.3390/ijms17101732

Complex complexity.Dionisio_{November 30, 2016
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[...] brain-enriched gangliosides, probably by their regulatory function on signalling, modulate neuronal function and contribute to neuronal development by influencing the epigenetic state of the cell. This regulatory layer adds to known mechanisms of tissue patterning such as morphogen gradients that induce the differentiation of specific cell types in a distinct spatial order.
Glycosphingolipid–Protein Interaction in Signal Transduction Domenico Russo, Seetharaman Parashuraman and Giovanni D’Angelo Int J Mol Sci. 17(10): 1732. doi: 10.3390/ijms17101732

Complex complexity.Dionisio_{November 30, 2016
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[...] the GSL composition of cells changes during differentiation, as a direct consequence of a change in the expression of specific GSL synthesizing enzymes. The transcriptional programmes responsible for these changes are unknown [...]
Glycosphingolipid–Protein Interaction in Signal Transduction Domenico Russo, Seetharaman Parashuraman and Giovanni D’Angelo Int J Mol Sci. 17(10): 1732. doi: 10.3390/ijms17101732

Complex complexity.Dionisio_{November 30, 2016
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GSLs constitute a regulatory layer acting orthogonally to the ligand–receptor–transducers module, which allows the dynamic fine-tuning of intracellular signalling. Vertebrates possess a vast repertoire of GSLs, which differ according to the sugar composition, the anomeric linkages of the glycosidic bonds, and to the extent of branching of their glycans. GSLs regulate cellular signalling pathways by interacting with components of the signal transduction machinery (i.e., hormones, receptors and, intracellular transducers).
Glycosphingolipid–Protein Interaction in Signal Transduction Domenico Russo, Seetharaman Parashuraman and Giovanni D’Angelo Int J Mol Sci. 17(10): 1732. doi: 10.3390/ijms17101732

Complex complexity.Dionisio_{November 30, 2016
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Glycosphingolipids (GSLs) are a class of ceramide-based glycolipids essential for embryo development in mammals. The synthesis of specific GSLs depends on the expression of distinctive sets of GSL synthesizing enzymes that is tightly regulated during development. [...] the mechanistic details of these GSL–protein interactions are often poorly understood [...] [...] the basic principles by which GSL-glycans are specifically perceived by GSDs are unknown.
Glycosphingolipid–Protein Interaction in Signal Transduction Domenico Russo, Seetharaman Parashuraman and Giovanni D’Angelo Int J Mol Sci. 17(10): 1732. doi: 10.3390/ijms17101732

Complex complexity.Dionisio_{November 30, 2016
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Both Petri nets and differential equations are important modeling tools for biological processes. In biology, a gradient is a graded change in concentration of specific signaling molecules, called morphogens, through a group of cells. The morphogens get produced by a cell or group of cells, called the source, and emanate from there spreading throughout the tissue. At the same time molecules get degraded in the tissue. This simultaneous production and degradation establishes a slope in concentration levels, known as the morphogen gradient. Cells in the tissue sense the morphogen concentration in their direct surroundings and respond by adopting a specific behavior. In this way morphogens have a direct effect on cell development and differentiation and are therefore of the utmost importance. For this reason, a model which furthers our understanding and analysis of the process, both from an operational as well as a denotational perspective, is of great use to the field of biology.
Modeling biological gradient formation: combining partial differential equations and Petri nets Laura M. F. Bertens, Jetty Kleijn, Sander C. Hille, Monika Heiner, Maciej Koutny and Fons J. Verbeek Nat Comput. 15(4): 665–675. doi: 10.1007/s11047-015-9531-4

Complex complexity. The authors of this paper should have consulted professor L. M. of the U. of T. in Canada who could have told them how exactly the morphogen gradients form. :)Dionisio_{November 30, 2016
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The brain enables animals to behaviorally adapt in order to survive in a complex and dynamic environment, but how reward-oriented behaviors are achieved and computed by its underlying neural circuitry is an open question. The BG have a parallel pathway structure suitable for conveying action commands, with both action promotion and suppression built in. [...] some PD symptoms could result from a dysfunctional D1 pathway, whereas the D2 pathway would still be functionally adequate although itself also affected by the reduced dopamine level.
Functional Relevance of Different Basal Ganglia Pathways Investigated in a Spiking Model with Reward Dependent Plasticity. Berthet P, Lindahl M, Tully PJ, Hellgren-Kotaleski J, Lansner A Front Neural Circuits. 10:53. doi: 10.3389/fncir.2016.00053.

Dionisio_{November 30, 2016
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When dealing with more complex reactions, such as reactions involving several components and several steps, our approach allows to recognize the various basic ‘devices’ at work and to build the whole circuitry in a cascade fashion so to figure out how the equivalent ‘electronic circuit’ effectively processes information as the reaction goes by. In particular, a suitable combination of the elementary bricks described above leads to the construction of (bio-)logic chemical gates [...] [...] efforts are still needed to enlarge this scheme in order to apply to general out-of-equilibrium regimes (for instance with time-dependent field variations).
Complete integrability of information processing by biochemical reactions Elena Agliari, Adriano Barra, Lorenzo Dello Schiavo and Antonio Moro Sci Rep. 6: 36314. doi: 10.1038/srep36314

[emphasis added] Complex complexity. :)Dionisio_{November 30, 2016
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Statistical mechanics provides an effective framework to investigate information processing in biochemical reactions. [...] how the thermodynamics of biochemical reactions spontaneously[?] encodes information processing. [?] These results stem from investigations scattered over different fields of biological research involving, for instance, inter-cellular and intra-cellular signalling, enzymatic cycles, ribo and toggle switches, ultra-sensitive mechanisms, DNA-computing, transcriptional and regulatory networks, and more.
Complete integrability of information processing by biochemical reactions Elena Agliari, Adriano Barra, Lorenzo Dello Schiavo and Antonio Moro Sci Rep. 6: 36314. doi: 10.1038/srep36314

[emphasis added] Complex complexity. :)Dionisio_{November 30, 2016
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MAP theory has the potential to provide a powerful framework to explore and understand the role of noise and dynamics in cell state transitions during normal development and also in other situations such as artificial directed reprogramming experiments. More generally, our results emphasise that stochastic fluctuations in gene expression can influence the dynamics and outcome of gene regulatory networks and highlight the importance of developing the mathematical tools to explore these aspects of developmental patterning.
Intrinsic Noise Profoundly Alters the Dynamics and Steady State of Morphogen-Controlled Bistable Genetic Switches. Perez-Carrasco R1, Guerrero P1, Briscoe J2, Page KM PLoS Comput Biol. 12(10):e1005154. doi: 10.1371/journal.pcbi.1005154.

Dionisio_{November 29, 2016
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A practical feature of MAP theory is that it can be extended to larger networks comprising several genes and to full kinetic reaction schemes, that include, for example, the dynamics of mRNA production and decay and discrete promoter states as well as more detailed description of the expression bursts [...]. This would offer insight not only into simple binary decisions, such as that described in this study, but also provide a way to study transitions in more complex and realistic models of cell development
Intrinsic Noise Profoundly Alters the Dynamics and Steady State of Morphogen-Controlled Bistable Genetic Switches. Perez-Carrasco R1, Guerrero P1, Briscoe J2, Page KM PLoS Comput Biol. 12(10):e1005154. doi: 10.1371/journal.pcbi.1005154.

Dionisio_{November 29, 2016
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Observing coordinated changes in gene expression that matched MAP predictions would support the validity of the MAP approach and allow key parameters of the biological system to be estimated. Experimental corroboration of gene expression dynamics characteristic of those predicted by the MAP would provide insight into the mechanisms controlling cell decisions and greatly strengthen the evidence underpinning the use of dynamical systems theory to model these developmental events.
Intrinsic Noise Profoundly Alters the Dynamics and Steady State of Morphogen-Controlled Bistable Genetic Switches. Perez-Carrasco R1, Guerrero P1, Briscoe J2, Page KM PLoS Comput Biol. 12(10):e1005154. doi: 10.1371/journal.pcbi.1005154.

Dionisio_{November 29, 2016
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A transcriptional mechanism capable of the analogue to digital conversion necessary to transform the continuous morphogen gradient into distinct domains of gene expression is the so-called genetic toggle switch. This sub-network, present in many biological contexts, consists of cross-repression between sets of transcriptional determinants that are expressed mutually exclusively in alternative cell identities.
Intrinsic Noise Profoundly Alters the Dynamics and Steady State of Morphogen-Controlled Bistable Genetic Switches. Perez-Carrasco R1, Guerrero P1, Briscoe J2, Page KM PLoS Comput Biol. 12(10):e1005154. doi: 10.1371/journal.pcbi.1005154.

Dionisio_{November 29, 2016
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The bistable switch, a common regulatory sub-network, is found in many biological processes. It consists of cross-repressing components that generate a switch-like transition between two possible states. In developing tissues, bistable switches, created by cross-repressing transcriptional determinants, are often controlled by gradients of secreted signalling molecules—morphogens. These provide a mechanism to convert a morphogen gradient into stripes of gene expression that determine the arrangement of distinct cell types.
Intrinsic Noise Profoundly Alters the Dynamics and Steady State of Morphogen-Controlled Bistable Genetic Switches. Perez-Carrasco R1, Guerrero P1, Briscoe J2, Page KM PLoS Comput Biol. 12(10):e1005154. doi: 10.1371/journal.pcbi.1005154.

Dionisio_{November 29, 2016
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During tissue development, patterns of gene expression determine the spatial arrangement of cell types. In many cases, gradients of secreted signalling molecules-morphogens-guide this process by controlling downstream transcriptional networks. A mechanism commonly used in these networks to convert the continuous information provided by the gradient into discrete transitions between adjacent cell types is the genetic toggle switch, composed of cross-repressing transcriptional determinants.
Intrinsic Noise Profoundly Alters the Dynamics and Steady State of Morphogen-Controlled Bistable Genetic Switches. Perez-Carrasco R1, Guerrero P1, Briscoe J2, Page KM PLoS Comput Biol. 12(10):e1005154. doi: 10.1371/journal.pcbi.1005154.

Dionisio_{November 29, 2016
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[...] the tonsils contribute to first line immunity against foreign pathogens in the upper aero-digestive tract [...] [...] the risk of deep neck infection is significantly increased among patients who have undergone a tonsillectomy. Additional research is needed to explore the possible mechanisms behind these findings.
Tonsillectomy and the Risk for Deep Neck Infection—A Nationwide Cohort Study Ying-Piao Wang,1,2,3 Mao-Che Wang,2,4 Hung-Ching Lin,1,3 Kuo-Sheng Lee,1,3 and Pesus Chou PLoS One. 10(4): e0117535. doi: 10.1371/journal.pone.0117535

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The human palatine tonsils and the nasopharyngeal tonsil were considered the defense mechanism against ingested or inhaled foreign pathogens. The current findings suggest that the tubal tonsils possess abilities of active transportation of foreign antigens, and will act as inductive and effector sites in the mucosal immune system. Our results also indicated a significant difference in roles of immune responses among individual tonsillar organs, suggesting functional sub-compartmentalization.
Functions of tonsils in the mucosal immune system of the upper respiratory tract using a novel animal model, Suncus murinus. Suzumoto M1, Hotomi M, Fujihara K, Tamura S, Kuki K, Tohya K, Kimura M, Yamanaka N Acta Otolaryngol. 126(11):1164-70. DOI: 10.1080/00016480600681593

Dionisio_{November 29, 2016
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The role of the human appendix is still not clearly identified. Recent literature shows that the human appendix might be regarded as a part of the immune system because many immunoglobulin-producing cells can be detected in normal appendix mucosa. Therefore, due to the change of immune function after removing the human appendix, people with appendectomy are found to be associated with increased risk of pulmonary tuberculosis, colorectal cancer, rheumatoid arthritis, and ischemic heart disease. More research is needed to examine issues related to the pathogenesis of appendectomy associated with pyogenic liver abscess.
Appendectomy correlates with increased risk of pyogenic liver abscess A population-based cohort study in Taiwan Kuan-Fu Liao, MD, MS,a,b Shih-Wei Lai, MD,c,d Cheng-Li Lin, MS,c,e and Sou-Hsin Chien, MDa Medicine (Baltimore). 95(26): e4015. doi: 10.1097/MD.0000000000004015

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The mechanism between the relationship with an appendectomy and subsequent disease still remains unknown. [...] female subjects who undergo an appendectomy have a higher risk of RA than comparison female subjects. The vermiform appendix is part of gut-associated lymphoid tissue (GALT) which may be considered an immune organ in a natural environment. Previous studies showed that changes in immune function after an appendectomy may be associated with a variety of diseases such as coeliac disease, ulcerative colitis, Crohn’s disease, Clostridium difficile infection, acute myocardial infraction, and pulmonary tuberculosis. Some evidence has shown that the appendix may be associated with substantial lymphatic tissue which is thought to play a specific role in immune function.
An Appendectomy Increases the Risk of Rheumatoid Arthritis: A Five-Year Follow-Up Study Ya-Mei Tzeng,#1 Li-Ting Kao,2 Senyeong Kao,2 Herng-Ching Lin,3 Ming-Chieh Tsai,#4 and Cha-Ze Lee PLoS One. 10(5): e0126816. doi: 10.1371/journal.pone.0126816

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[...] the risk of gallstones was significantly higher for patients within 5 years after an appendectomy. The specific pathway linking an appendectomy to gallstone formation, especially in women, deserves attention and further study. Future more extensive investigations possibly collecting laboratory investigations in longitudinal follow-up study design with larger sample sizes are warranted to further ascertain the link between appendectomy and its consequent risks on gallstones. [...] the appendix is recognized as an essential component of mammalian mucosal immune function, particularly B-lymphocyte-mediated immune responses and extrathymically derived T-lymphocytes. As one of the guardians of the internal body from the hostile external environment being removed after an appendectomy, the "safe house" for commensal bacteria is damaged. Impaired immunity may facilitate proliferation of pathogens which induce regional infectious diseases, such as Crohn’s disease. Further clinical or basic studies are needed to elucidate whether gallstones are consequences or comorbidities of appendicitis/an appendectomy.
Increased Risk of Clinically Significant Gallstones following an Appendectomy: A Five-Year Follow-Up Study Shiu-Dong Chung,#1,2,3 Chung-Chien Huang,#4 Herng-Ching Lin,#3,4 Ming-Chieh Tsai,5 and Chao-Hung Chen PLoS One. 11(10): e0165829. doi: 10.1371/journal.pone.0165829

[emphasis added]Dionisio_{November 29, 2016
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The real function of the human appendix has long been argued. Although it might not be considered vital, recent studies have observed an association between removal of the appendix and GI tract diseases, such as an elevated risk for Crohn’s disease and a reduced risk for ulcerative colitis. In a population-based study, increased risks of malignancy in digestive systems, such as colorectal cancer, were found following an appendectomy. Moreover, the incidence of gall bladder cancer increased 2-fold among patients who underwent an appendectomy.
Increased Risk of Clinically Significant Gallstones following an Appendectomy: A Five-Year Follow-Up Study Shiu-Dong Chung,#1,2,3 Chung-Chien Huang,#4 Herng-Ching Lin,#3,4 Ming-Chieh Tsai,5 and Chao-Hung Chen PLoS One. 11(10): e0165829. doi: 10.1371/journal.pone.0165829

Dionisio_{November 29, 2016
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Findings suggest that the appendix is well-suited to serve as a “safe house” for biofilm formation to preserve and protect commensal bacteria needed in the colon. More evidence has accumulated associating an appendectomy with chronic inflammatory disorders of the gastrointestinal (GI) tract closer to the appendix, such as ulcerative colitis and Crohn’s disease. Cancer risks following an appendectomy were also observed in GI tract systems including colon cancer and the reproductive system including prostate cancer
Increased Risk of Clinically Significant Gallstones following an Appendectomy: A Five-Year Follow-Up Study Shiu-Dong Chung,#1,2,3 Chung-Chien Huang,#4 Herng-Ching Lin,#3,4 Ming-Chieh Tsai,5 and Chao-Hung Chen PLoS One. 11(10): e0165829. doi: 10.1371/journal.pone.0165829

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