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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The PTK7 receptor functions in various processes ranging from embryonic morphogenesis to wound repair and its distinct functions are likely regulated by receptor context. [...] an interaction with bona fide non-canonical Wnt receptors has so far not been analyzed. Both, PTK7 and Ror2 possess Ig-like domains, which mediate a large variety of protein-protein interactions. However, we can currently not rule out that there may be additional interaction sites. [...] [...] it remains unclear if this interaction is direct or for example mediated by Wnt ligands or Frizzled co-receptors. [...] the exact molecular composition of a PTK7/Ror2 receptor complex remains yet to be analyzed, [...] The downstream signaling events of the PTK7/Ror2 complex are currently unclear, [...] For PTK7 the mechanism of JNK activation remains unclear, [...] [...], PTK7 and Ror2 share a function in the inhibition of canonical Wnt signaling, [...] The molecular mechanisms are currently unclear. Currently it remains unclear by which mechanism a PTK7/Ror2 complex affects NC migration. [...] Ror2 is capable to compensate for both putative functions of PTK7. Therefore, it remains to be seen which one of these or if possibly even a combination of both is required.
Podleschny M, Grund A, Berger H, Rollwitz E, Borchers A (2015) A PTK7/Ror2 Co-Receptor Complex Affects Xenopus Neural Crest Migration. PLoS ONE 10(12): e0145169. doi:10.1371/journal.pone.0145169 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145169

The more we know, more is ahead for us to learn. Complex complexity. Work in progress… stay tuned.Dionisio_{January 31, 2016
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Future studies will have to assess how PTK7 and ROR2 cross-talk within the heterodimeric complex at the signaling and functional levels.
The PTK7 and ROR2 Protein Receptors Interact in the Vertebrate WNT/Planar Cell Polarity (PCP) Pathway Sébastien Martinez, Pierluigi Scerbo, Marilyn Giordano, Avais M. Daulat, Anne-Catherine Lhoumeau, Virginie Thomé, Laurent Kodjabachian, and Jean-Paul Borg doi: 10.1074/jbc.M115.697615 The Journal of Biological Chemistry, 290, 30562-30572. http://www.jbc.org/content/290/51/30562.full#content-block

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[...] Pkdcc1 is able to induce a luciferase reporter under the control of Atf2 promoter. Surprisingly, Pkdcc2 is not able to induce the activation of this reporter but, contrary, it is able to inhibit its normal activation by Wnt11 or Wnt5a. [...] despite the similarities observed between their phenotypes, Pkdcc1 and Pkdcc2 have different roles in JNK dependent PCP signaling pathway. [...] two members of PKDCC family, X. laevis Pkdcc1 and Pkdcc2 proteins are involved in the regulation of JNK dependent PCP signaling
Vitorino M, Silva AC, Inácio JM, Ramalho JS, Gur M, Fainsod A, et al. (2015) Xenopus Pkdcc1 and Pkdcc2 Are Two New Tyrosine Kinases Involved in the Regulation of JNK Dependent Wnt/PCP Signaling Pathway. PLoS ONE 10(8): e0135504. doi:10.1371/journal.pone.0135504 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0135504

The more we know, more is ahead for us to learn. Complex complexity. Work in progress… stay tuned.Dionisio_{January 31, 2016
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Wnt signaling pathways act at multiple locations and developmental stages to specify cell fate and polarity in vertebrate embryos. A long-standing question is how the same molecular machinery can be reused to produce different outcomes. The canonical Wnt/?-catenin branch modulates target gene transcription to specify cell fates along the dorsoventral and anteroposterior embryonic axes. By contrast, the Wnt/planar cell polarity (PCP) branch is responsible for cell polarization along main body axes, which coordinates morphogenetic cell behaviors during gastrulation and neurulation. Whereas both cell fate and cell polarity are modulated by spatially- and temporally-restricted Wnt activity, the downstream signaling mechanisms are very diverse. This review highlights recent progress in the understanding of Wnt-dependent molecular events leading to the establishment of PCP and linking it to early morphogenetic processes.
Spatial and temporal aspects of Wnt signaling and planar cell polarity during vertebrate embryonic development Sergei Y. Sokol Seminars in Cell & Developmental Biology Volume 42, Pages 78–85 Claudins and Time, Space and the Vertebrate Body Axis http://www.sciencedirect.com/science/article/pii/S1084952115000993

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Nutrient-sensing signals could be key architects of transcriptional circuitry by controlling almost every facet of signaling, transcription, translation, and other cellular functions that impinge on lineage choices. A major unanswered question raised by these findings is what cellular component is responsible for the apparent disparity in PI3K signaling intensity we observe? It also remains to be determined why initial divisions of naive lymphocytes do not appear to achieve PI3K thresholds sufficient to inactivate FoxO1 or induce IRF4 to the maximal intensity observed in later divisions. Identification of the actual asymmetrically inherited molecule(s) or organelle(s) governing the discrepant intensities will be required to resolve this issue. Pattern formation in development occurs when a small number of cells, with limited diversity, assume greater heterogeneity and complex arrangement in space and time as the cellularity of an embryo or tissue expands. Whether this mechanism will be more common in cellular expansion of mobile cells than in fixed tissue, only seen in the context of rapid cell division, or emerge only as a property of PI3K signaling remains to be determined.
Asymmetric PI3K Signaling Driving Developmental and Regenerative Cell Fate Bifurcation Wen-Hsuan W. Lin,1,4 William C. Adams,1,4 Simone A. Nish,1 Yen-Hua Chen,1 Bonnie Yen,1 Nyanza J. Rothman,1 Radomir Kratchmarov,1 Takaharu Okada,2 Ulf Klein,3 and Steven L. Rainer DOI: http://dx.doi.org/10.1016/j.celrep.2015.10.072 Volume 13, Issue 10, p2203–2218

The more we know, more is ahead for us to learn. Complex complexity. Work in progress… stay tuned.Dionisio_{January 31, 2016
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Although the generation of long-lived memory lymphocytes is an essential feature of an adaptive immune response, the fundamental question of when and how these cells arise has remained controversial. [...] single-cell gene expression approaches undertaken by investigators across scientific disciplines, along with ever-improving advances in such technologies as single-cell RNA sequencing45,46 and single-cell mass cytometry47, will continue to provide unprecedented molecular insights into cell fate specification in diverse biological settings [...]
Early specification of CD8+ T lymphocyte fates during adaptive immunity revealed by single-cell gene-expression Analysis Janilyn Arsenio,1, 4, Boyko Kakaradov,2, 4, Patrick J Metz,1, Stephanie H Kim,1, Gene W Yeo2, 3, & John T Chang Nature Immunology Volume:15, Pages:365–372 DOI:doi:10.1038/ni.2842

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Naïve CD8+ T lymphocytes responding to microbial pathogens give rise to effector T cells that provide acute defense and memory T cells that provide long-lived immunity. A single naïve CD8+ T lymphocyte can give rise to both effector and memory T cell subsets during a microbial infection. [...] the ontology of these various CD8+ T lymphocytes subsets remains poorly understood. Balancing the numbers of effector and memory T lymphocytes is essential for generating an optimal adaptive immune response that can provide acute and long-term protection against microbial pathogens. [...] alternative markers should be explored to more precisely study the heterogeneous populations of CD8+ T lymphocytes present during an adaptive immune response. [...] asymmetric division plays a critical role in regulating early specification of effector and memory fates and the generation an optimal adaptive immune response.
Regulation of Asymmetric Division by Atypical Protein Kinase C Influences Early Specification of CD8+ T Lymphocyte Fates Patrick J. Metz1, Justine Lopez1, Stephanie H. Kim1, Kazunori Akimoto2, Shigeo Ohno2 & John T. Chang Scientific Reports 6, Article number: 19182 (2016) doi:10.1038/srep19182 http://www.nature.com/articles/srep19182

The more we know, more is ahead for us to learn. Complex complexity. Work in progress… stay tuned.Dionisio_{January 31, 2016
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MicroRNAs are small non-coding RNAs that participate in different biological processes, providing subtle combinational regulation of cellular pathways, often by regulating components of signalling pathways. Significantly, the number of validated targets of each of the myomiRs has increased greatly in recent years, yet the extent to which each myomiR, miR-133, miR-1 or miR-206, contributes to specific tumorigenesis or tumor progression must await fuller clarification and integration with complex cellular regulatory pathway processes which are not yet fully defined.
Roles of the canonical myomiRs miR-1, -133 and -206 in cell development and disease Keith Richard Mitchelson, Wen-Yan Qin World J Biol Chem. 6(3): 162-208 doi: 10.4331/wjbc.v6.i3.162

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[...] it is likely that Nedd4 regulates target proteins differentially in a cell type-specific manner. [...] whether this or other targets of Nedd4 play important roles in osteoblast growth dynamics remain to be explored. [...] provide an ideal resource to explore the cell-intrinsic mechanisms of neural crest cells in craniofacial morphogenesis.
Cell autonomous roles of Nedd4 in craniofacial bone formation Sophie Wiszniak, Natasha Harvey, Quenten Schwarz doi:10.1016/j.ydbio.2015.12.001 Developmental Biology Volume 410, Issue 1, Pages 98–107 http://www.sciencedirect.com/science/article/pii/S001216061530066X

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The molecular basis for SPB-driven Tem1 activation remains elusive. [...] Tem1 inactivation causes only spindle orientation defects [...] Tem1 hyperactivation causes in addition spindle mispositioning [...] The molecular bases of this difference remain to be established. One crucial question that remains unsolved is how Tem1 activity toward mitotic exit is restrained until telophase while being already operational in metaphase toward spindle positioning. Another important issue that remains to be addressed is what triggers Tem1 activation at SPBs.
Coupling spindle position with mitotic exit in budding yeast: The multifaceted role of the small GTPase Tem1 DOI: 10.1080/21541248.2015.1109023 Ilaria Scarfoneab & Simonetta Piattia* pages 1-6, Small GTPases Volume 6, Issue 4, 2015k

The more we know, more is ahead for us to learn. Complex complexity. Work in progress… stay tuned.Dionisio_{January 25, 2016
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Spindle alignment directs the plane of cytokinesis, and alignment in the plane of the epithelial tissue promotes tissue growth and spreading, whereas perpendicular spindle alignment redirects the plane of cytokinesis. Redirection of the plane of cytokinesis when the spindle aligns perpendicularly to epithelium can lead to defective tissue morphogenesis, because the plane of cytokinesis determines the relative position of daughter cells produced by mitosis. It may be speculated that impaired mitotic rounding and misalignment of the mitotic spindle independently or synergistically influence cellular viability. [...] the contributions of proteins involved in mitotic cell rounding to generating force can be quantified by combining the micropillar assay with targeted chemical perturbation.
Mitotic cells contract actomyosin cortex and generate pressure to round against or escape epithelial confinement Barbara Sorce,1, Carlos Escobedo,1, 2, Yusuke Toyoda,3, Martin P. Stewart,1, 4, 5, Cedric J. Cattin,1, Richard Newton,1, Indranil Banerjee,6, Alexander Stettler,1, Botond Roska,6, Suzanne Eaton,3, Anthony A. Hyman,3, Andreas Hierlemann1, & Daniel J. Müller1, Nature Communications Volume:6, Article number:8872 DOI:doi:10.1038/ncomms9872 http://www.nature.com/ncomms/2015/151125/ncomms9872/abs/ncomms9872.html

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In the past several years, we have made significant progress in dissecting the functional roles of the cadherins and catenins in various aspects of neuronal morphogenesis and synaptic plasticity. However, several exciting questions remain. [...] it is not entirely clear how the catenins contribute to the functional roles of the non-classical cadherins in central neurons. [...] knowledge of the contribution of the cadherin catenin complex to inhibitory synaptogenesis remains incomplete. Accepting the challenge of dissecting out these signaling pathways and functional roles may lead to critical insights into the functional roles of these proteins in central neurons. The challenge is to determine the identity of stimuli specific signaling pathways, their outcomes and contribution to neuronal development and neurological disorders. [...] the next several years will bring forth a cascade of data that will significantly enhance our understanding of the role of the cadherin-catenin complex in central neurons [...]
Cadherins and catenins in dendrite and synapse morphogenesis DOI: 10.4161/19336918.2014.994919 Eunju Seonga, Li Yuanb & Jyothi Arikkathab* Cell Adhesion & Migration Volume 9, Issue 3, 2015 pages 202-213 http://www.tandfonline.com/doi/abs/10.4161/19336918.2014.994919?src=recsys

The more we know, more is ahead for us to learn. Complex complexity. Work in progress… stay tuned.Dionisio_{January 23, 2016
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Asymmetric cell division (ACD) can be viewed as a four-step process. In a first step, the mother cell acquires and/or re-orients a polarity axis. Second, cell fate determinants, i.e. molecules and/or organelles that are unequally inherited and that have the ability to influence the fate of the daughter cells, are distributed in a polar manner in the mitotic cell. Third, the mitotic spindle lines up along the cell polarity axis so that fate determinants become asymmetrically segregated at cytokinesis. In a fourth step, these fate determinants regulate a binary fate choice to implement fate asymmetry. Numb is a conserved multifunctional protein [involved in] regulating a wide range of processes, from intracellular trafficking to proteasome-mediated degradation. Several questions, however, remain. Future studies will certainly shed new light on how Numb inhibits Notch at the molecular level. This novel function of Neur raises two questions. First, does Neur regulate apical–basal polarity in SOPs and, second, is the Neur-dependent signaling by Dl functionally coupled to a change in apical–basal polarity in SOPs. Addressing these issues may shed new light on how signaling and cell polarity are coupled in the context of ACD. However, whether Dl is the relevant target of Sec15 in pIIb, whether Rab11 regulates the activity of Dl in pIIb and whether the recycling of Dl is necessary for its signaling activity remain to be clarified. Thus, further investigation may be needed to test the relevance of this model. [...] further studies are needed to test the role of the directional trafficking of Sara-positive endosomes for Notch activity in pIIa. [...] whether centrosome asymmetry and inheritance occur in SOPs and contribute to fate asymmetry remains to be studied. The unequal segregation of Numb and Neur relies on their polar localization at mitosis. The mechanism whereby Numb localizes at the anterior cortex is relatively well understood and involves an inhibitory phosphorylation mechanism. The cortical exclusion of Numb by a phosphorylation-dependent mechanism regulated by aPKC provides an elegant control mechanism for the polar distribution of Numb at mitosis. Whether a similar mechanism regulates the anterior accumulation of Neur remains to be tested. This mechanism may, however, be general since the localization of the cell fate determinant Miranda is regulated by this mechanism. Whether aPKC phosphorylates Baz in SOPs, whether phosphorylated Baz forms an active complex with Par6-aPKC at the posterior cortex and whether this regulation is important for the recruitment and phosphorylation of Numb remain to be studied. A key and largely unanswered question remains: when and how does the Baz-Par6-aPKC complex localize at the posterior cortex? [...] whether planar polarization of active aPKC is established at mitosis or prior to mitosis remains to be determined. [...] it is thought that a PCP-independent mechanism breaks the planar symmetry of SOPs. The nature of this symmetry-breaking cue is unknown. [...] a mutual antagonism might underlie this symmetry-breaking activity to create two opposite Pins- and Baz-containing complexes. The molecular basis of this antagonism and the mechanisms ensuring that this antagonism operates within the plane of the epithelium (rather than along the apical–basal axis) and at mitosis (and not before) are not known. Whether this antagonism is sufficient to establish asymmetry at mitosis in the absence of PCP remains to be determined. [...] whether mitotic kinases, [...], might regulate symmetry breaking by modulating this mutual antagonism remains to be investigated. How PCP provides this bias is unclear but molecular interactions between core PCP proteins and components of the Baz-Par6-aPKC complex may provide entry points into this question. Whether junction remodeling is required for the planar polarization of SOPs and, more generally, for ACD in epithelia, is an open question.
Asymmetric cell division in the Drosophila bristle lineage: from the polarization of sensory organ precursor cells to Notch-mediated binary fate decision François Schweisguth DOI: 10.1002/wdev.175 Wiley Interdisciplinary Reviews: Developmental Biology Volume 4, Issue 3, pages 299–309 http://onlinelibrary.wiley.com/doi/10.1002/wdev.175/full

The more we know, more is ahead for us to learn. Complex complexity. Work in progress... stay tuned. [emphasis mine]Dionisio_{January 23, 2016
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ESCs have been shown to employ unique mechanisms to maintain a more-stable genome than somatic cells, including efficient DNA repair, elimination of damaged cells, antioxidant defense, and suppression of mutagenesis. Our study adds a new dimension to these unique properties by showing that ESCs use more DOs to effectively protect their genomes from replication stress and ensure their genome integrity. It remains elusive how ESCs recruit a larger number of DOs than tissue stem/progenitor cells during DNA licensing. Future studies in other tissue stem cells in the Mcm4C/C mice will allow further understanding of the growth retardation and other deficiencies associated with the hypomorphic MCM4 conditions in human patients.
Embryonic Stem Cells License a High Level of Dormant Origins to Protect the Genome against Replication Stress Xin Quan Ge, Jinah Han, Ee-Chun Cheng, Satoru Yamaguchi, Naoko Shima, Jean-Leon Thomas, Haifan Lin DOI: http://dx.doi.org/10.1016/j.stemcr.2015.06.002 Stem Cell Reports Volume 5, Issue 2, p185–194 http://www.cell.com/stem-cell-reports/fulltext/S2213-6711(15)00183-6

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Spatiotemporal patterns of DNA replication have been described for yeast and many types of cultured animal cells, frequently after cell cycle arrest to aid in synchronization. However, patterns of DNA replication in nuclei from plants or naturally developing organs remain largely uncharacterized. [...] maize euchromatin exists as an intermingled mixture of two components distinguished by their condensation state and replication timing. These different patterns might reflect a previously described genome organization pattern, with “gene islands” mostly replicating during early S phase followed by most of the intergenic repetitive regions replicating during middle S phase.
Defining multiple, distinct, and shared spatiotemporal patterns of DNA replication and endoreduplication from 3D image analysis of developing maize (Zea mays L.) root tip nuclei Hank W. Bass, Gregg G. Hoffman, Tae-Jin Lee, Emily E. Wear, Stacey R. Joseph, George C. Allen, Linda Hanley-Bowdoin, William F. Thompson 10.1007/s11103-015-0364-4 http://link.springer.com/article/10.1007/s11103-015-0364-4/fulltext.html

Complex complexity Work in progress... stay tunedDionisio_{January 6, 2016
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Both appear to rely on spatial control of Aurora B activity, but the precise molecular basis for this spatial control remains unknown. Future analyses will have to rigorously test the implications of the models that have been proposed to explain the spatial regulation of Aurora B activity, including the “centromere gradient” model and the “dog leash” model. It is hoped that global analyses of Aurora B substrate phosphorylation within the framework of predictable alterations of CPC and kinetochore function will finally shed light on the molecular basis of a mechanism that is indispensable for life.
The Aurora B kinase in chromosome bi-orientation and spindle checkpoint signaling Veronica Krenn and Andrea Musacchio Front. Oncol., http://dx.doi.org/10.3389/fonc.2015.00225 http://journal.frontiersin.org/article/10.3389/fonc.2015.00225/full

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Chromosome bi-orientation is a critical requirement for accurate chromosome segregation during mitosis and requires that both kinetochores are stably attached to spindle microtubules. Tension from spindle forces has long been known to stabilize correct kinetochore-microtubule attachments (King and Nicklas, 2000), but how the first end-on attachments are stabilized before the development of tension has remained unknown. Polar ejection forces (PEFs) generated by Chromokinesins promoted the conversion from lateral to end-on kinetochore-microtubule attachments that satisfied the SAC in SMUGs. Thus, PEFs convert lateral to stable end-on kinetochore-microtubule attachments, independently of chromosome bi-orientation.
Polar Ejection Forces Promote the Conversion from Lateral to End-on Kinetochore-Microtubule Attachments on Mono-oriented Chromosomes Danica Drpic, António J. Pereira, Marin Barisic, Thomas J. Maresca, Helder Maiato DOI: http://dx.doi.org/10.1016/j.celrep.2015.08.008 http://www.cell.com/cell-reports/abstract/S2211-1247(15)00864-5 http://www.cell.com/cell-reports/fulltext/S2211-1247(15)00864-5

Complex complexity Work in progress... stay tunedDionisio_{January 4, 2016
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Cytoplasmic dynein associates with dynactin to drive cargo movement on microtubules, but the structure of the dynein–dynactin complex is unknown. Using electron microscopy, we determined the organization of native bovine dynein, dynactin and the dynein–dynactin–microtubule quaternary complex. In the microtubule-bound complex, the dynein motor domains are positioned for processive unidirectional movement, and the cargo-binding domains of both dynein and dynactin are accessible. Although more detailed structural information will certainly improve understanding of the mechanism of dynein-dynactindependent movement, high-resolution determination of this entire structure will be extremely challenging due to the large size of the DDB complex and the heterogeneity of its link to the MT surface. The organizational framework of the DDB complex presented here provides the foundation for future work that supplies a new structural context for interpreting decades of biophysical and biochemical studies aimed at deciphering the mechanics of this fundamental and ancient cellular transport system.
Structural organization of the dynein–dynactin complex bound to microtubules Saikat Chowdhury, Stephanie A Ketcham, Trina A Schroer & Gabriel C Lander Nature Structural & Molecular Biology 22, 345–347 (2015) doi:10.1038/nsmb.2996 http://www.nature.com/nsmb/journal/v22/n4/full/nsmb.2996.html

Emphasis mine. Complex complexity Work in progress... stay tunedDionisio_{January 4, 2016
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This inherent flexibility of the dynein motor, and the quasi-independent flexibility of the two motors of offset dimers, implies that it is wrong to imagine stepping dynein as having a single structure, even when both motors are attached to the MT. It will therefore be a challenge to determine the structure of any dynein-MT complex at high resolution, since current methods for this all combine data from many molecules. Dynein flexibility also raises new questions about the nature of the allosteric communication between the ATPase cycle in the head and the MT binding affinity of the stalkhead that is vital to dynein’s many cellular functions.
Direct observation shows superposition and large scale flexibility within cytoplasmic dynein motors moving along microtubules Hiroshi Imai, Tomohiro Shima, Kazuo Sutoh, Matthew L. Walker, Peter J. Knight, Takahide Kon & Stan A. Burgess Nature Communications 6, Article number: 8179 doi:10.1038/ncomms9179 http://www.nature.com/ncomms/2015/150914/ncomms9179/full/ncomms9179.html

Complex complexity Work in progress... stay tunedDionisio_{January 4, 2016
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[...] key questions remain regarding how Ipl1 phosphorylation of Dam1p regulates the kinetochore–MT interface during mitosis. [...] the specific regions involved in the MT-binding interface have not been identified and the localization of half of the subunits remains unknown. Whereas the majority of the cross-links between the Dam1 complex and the MT occur with ?-tubulin [...], the majority of the Ska1 cross-links to the MT occur with ?-tubulin31. Further work is necessary to resolve the significance of these differences. As phosphorylating the Dam1p C terminus mildly decreases the Dam1 complex’s affinity to MTs, it is likely to be that this domain contains multiple functions that can be deciphered by further investigation.
The molecular architecture of the Dam1 kinetochore complex is defined by cross-linking based structural modelling Alex Zelter, Massimiliano Bonomi, Jae ook Kim, Neil T. Umbreit, Michael R. Hoopmann, Richard Johnson, Michael Riffle, Daniel Jaschob, Michael J. MacCoss, Robert L. Moritz & Trisha N. Davis Nature Communications 6, Article number: 8673 doi:10.1038/ncomms9673 http://www.nature.com/ncomms/2015/151112/ncomms9673/full/ncomms9673.html

Complex complexity Work in progress... stay tunedDionisio_{January 4, 2016
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Accurate segregation of chromosomes during cell division is essential. Understanding the roles and regulation of the Dam1 complex requires structural information. The kinetochore is a network of protein complexes that assemble on centromeric DNA and mediate the attachment of chromosomes to dynamic spindle microtubules (MTs). Intricate error-correction mechanisms exist to prevent such errors and delay cell cycle progression until correct kinetochore–MT attachments are achieved.
The molecular architecture of the Dam1 kinetochore complex is defined by cross-linking based structural modelling Alex Zelter, Massimiliano Bonomi, Jae ook Kim, Neil T. Umbreit, Michael R. Hoopmann, Richard Johnson, Michael Riffle, Daniel Jaschob, Michael J. MacCoss, Robert L. Moritz & Trisha N. Davis Nature Communications 6, Article number: 8673 doi:10.1038/ncomms9673 http://www.nature.com/ncomms/2015/151112/ncomms9673/full/ncomms9673.html

Complex complexity Work in progress... stay tunedDionisio_{January 4, 2016
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Proper chromosome segregation during mitosis relies on correct kinetochore–microtubule (KT–MT) interaction. [...] it remains a mystery how, despite KT-MT attachments being weakened and disrupted by Aurora [...], new attachments can be formed efficiently [...], ensuring the KT–MT turnover. [...] it has long been unclear how new attachments can still be formed, and errors corrected, despite attachment being weakened and disrupted by Aurora B. How does Aurora B specifically disrupt end-on attachment without affecting lateral attachment? [...] a transition from low– to high–tension state still remains a mystery. [...] we speculate that end-on, but not lateral, attachment is regulated by Aurora B in metazoan cells, similarly to budding yeast.
Kinetochore–microtubule error correction is driven by differentially regulated interaction modes Maria Kalantzaki, Etsushi Kitamura, Tongli Zhang, Akihisa Mino, Béla Novák & Tomoyuki U. Tanaka Nature Cell Biology 17, 421–433 (2015) doi:10.1038/ncb3128 http://www.nature.com/ncb/journal/v17/n4/full/ncb3128.html

Complex complexity Work in progress... stay tunedDionisio_{January 3, 2016
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For proper chromosome segregation, sister kinetochores must interact with microtubules from opposite spindle poles (bi-orientation). To establish bi-orientation, aberrant kinetochore–microtubule attachments are disrupted (error correction) by ?aurora B kinase (?Ipl1 in budding yeast). Paradoxically, during this disruption, new attachments are still formed efficiently to enable fresh attempts at bi-orientation. How this is possible remains an enigma.
Kinetochore–microtubule error correction is driven by differentially regulated interaction modes Maria Kalantzaki, Etsushi Kitamura, Tongli Zhang, Akihisa Mino, Béla Novák & Tomoyuki U. Tanaka Nature Cell Biology 17, 421–433 (2015) doi:10.1038/ncb3128 http://www.nature.com/ncb/journal/v17/n4/full/ncb3128.html

Complex complexity Work in progress... stay tunedDionisio_{January 3, 2016
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Sophisticated signaling networks are required for development and survival, and a minor disruption of any of these pathways may cause severe diseases such as cancer in humans. The technological advancement in the field of AP/MS analysis for proteomics studies is far exceeding our ability to handle the information properly. Moreover, the field of mathematical modeling is also growing fast. We hope that one day data produced by all different platforms will be integrated into one database and generate a super-interactive network for signaling pathways, which truly reflect the complex biological systems we are working on.
From pathways to networks: Connecting dots by establishing protein–protein interaction networks in signaling pathways using affinity purification and mass spectrometry Xu Li, Wenqi Wang, Junjie Chen DOI: 10.1002/pmic.201400147 PROTEOMICS Special Issue: Signal Transduction Volume 15, Issue 2-3 Pages 188–202 http://onlinelibrary.wiley.com/doi/10.1002/pmic.201400147/abstract

Complex complexity Work in progress... stay tunedDionisio_{January 3, 2016
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Protein–protein interactions are at the core of all cellular functions and dynamic alterations in protein interactions regulate cellular signaling. Future challenges remain in mapping transient protein interactions after cellular perturbations as well as in resolving the spatial organization of protein interaction networks. Future challenges remain in the identification of transient and low affinity interactions during cellular signaling, as well as in understanding the spatial organization of protein interaction networks.
Illuminating Spatial and Temporal Organization of Protein Interaction Networks by Mass Spectrometry-Based Proteomics Jiwen Yang, Sebastian A. Wagner and Petra Beli Front. Genet., http://dx.doi.org/10.3389/fgene.2015.00344

Complex complexity Work in progress... stay tunedDionisio_{January 3, 2016
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Resveratrol prevents hepatic steatosis and endoplasmic reticulum stress and regulates the expression of genes involved in lipid metabolism, insulin resistance, and inflammation in rats http://www.sciencedirect.com/science/article/pii/S0271531715001013 Resveratrol ameliorates hepatic steatosis and inflammation in methionine/choline-deficient diet-induced steatohepatitis through regulating AutoPlay http://lipidworld.biomedcentral.com/articles/10.1186/s12944-015-0139-6 A high practice rate seems to be the most important factor for physical fitness improvement and fat mass loss. Health benefits appear at 78 minutes of brisk walk per week and increase with adherence to training, in moderately obese and initially sedentary, postmenopausal women. http://www.sciencedirect.com/science/article/pii/S1877065715000536 Changes of salivary estrogen levels for detecting the fertile period http://www.sciencedirect.com/science/article/pii/S0301211515002687Dionisio_{January 3, 2016
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[...] probiotics have limited efficacy in terms of decreasing body weight and BMI and were not effective for weight loss. [...] more rigorously designed RCTs are necessary to examine the effect of probiotics on body weight in greater detail.
Probiotics for weight loss: a systematic review and meta-analysis ? Sunmin Park, Ji-Hyun Bae doi:10.1016/j.nutres.2015.05.008 Nutrition Research Volume 35, Issue 7, Pages 566–575 http://www.sciencedirect.com/science/article/pii/S0271531715001037

Complex complexity Work in progress... stay tunedDionisio_{January 3, 2016
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The human gastrointestinal tract contains bacterial species that, among other functions, maintain a microbial barrier against potential pathogens and help regulate the immune response in the human body. The composition of gut microbiota and its variations hold an important role in the development of liver diseases. Under pathological conditions, bacterial components are released into the liver–gut axis and cause proinflammatory and autoimmune responses in the liver; these responses can initiate direct damage to liver cells. Probiotics have been shown to have favorable effects when used to treat several liver diseases by reducing the production of bacterial toxins and by modulating autoimmune responses, intestinal permeability, and the inflammatory response.
Current evidence on the use of probiotics in liver diseases Norberto C. Chávez-Tapia, Leticia González-Rodríguez, MinSeung Jeong, Yanine López-Ramírez, Varenka Barbero-Becerra, Eva Juárez-Hernández, Juan L. Romero-Flores, Marco Arrese, Nahúm Méndez-Sánchez, Misael Uribe doi:10.1016/j.jff.2015.05.009 Journal of Functional Foods Volume 17, Pages 137–151 http://www.sciencedirect.com/science/article/pii/S1756464615002467

Complex complexity Work in progress... stay tunedDionisio_{January 3, 2016
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Our strategy involved investigation on understanding the chemistry behind the antioxidant activities of BHT, whether through hydrogen or electron transfer mechanism to enable promising anti-oxidant candidates to be synthesized.
Understanding the chemistry behind the antioxidant activities of butylated hydroxytoluene (BHT): A review Wageeh A. Yehye, Noorsaadah Abdul Rahman, Azhar Ariffin, Sharifah Bee Abd Hamid, Abeer A. Alhadi, Farkaad A. Kadir, Marzieh Yaeghoobi doi:10.1016/j.ejmech.2015.06.026 http://www.sciencedirect.com/science/article/pii/S022352341530101X

Complex complexity Work in progress... stay tunedDionisio_{January 3, 2016
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Chitosan and COS due to their antioxidant, anti-inflammatory, antidiabetic, and anticancer properties show promising potential to be used in prevention, delay, mitigation and treatment of age-related dysfunctions and diseases. Development of novel COS derivatives such as sulfated, carboxylated and phenolic acid conjugated COS and their application in novel nanoparticulated systems, functional foods, and nutraceuticals can essentially increase bioavailability and stability of bioactive components. Mucoadhesive films containing chitosan-coated nanoparticles can find novel applications in nanomedicine. Breakthrough results in delay and prevention of age-related dysfunctions can be expected in the future.
The Potential of Chitosan and Its Derivatives in Prevention and Treatment of Age-Related Diseases Garry Kerch Mar. Drugs 2015, 13(4), 2158-2182; doi:10.3390/md13042158 http://www.mdpi.com/1660-3397/13/4/2158/htm

Complex complexity Work in progress... stay tunedDionisio_{January 3, 2016
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