Uncommon Descent Serving The Intelligent Design Community

Rethinking biology: What role does physical structure play in the development of cells?

Share
Facebook
Twitter
LinkedIn
Flipboard
Print
Email

That’s structuralism, in part. Further to Evelyn Fox Keller’s comment that the landscape of biological thought is being “radically reconfigured,” a cancer geneticist writes to say that a tumor’s physical environment fuels its growth and causes treatment resistance:

The forces of cancer

In vitro experiments showing that cancer cells actively migrate in response to fluid flow have supported the hypothesis that fluid escaping from the boundary of a tumor may guide the invasive migration of cancer cells toward lymphatic or blood vessels, potentially encouraging metastasis. There remains controversy over how the fluid forces induce the migration; the cells may respond to chemical gradients created by the cells and distorted by the flowing fluid,8 or the fluid may activate cell mechanosensors. Because of the potential for new therapeutic interventions, the transduction of mechanical fluid forces into biochemical signals by cell mechanosensors is an active area of investigation. In a more direct manner, the fluid flow can physically carry cancer cells to lymph nodes.

And fluid pressure is just one of the many forces in a tumor that can influence its development and progression. Tumors also develop increased solid pressure, as compared with normal tissue, stemming from the uncontrolled division of cancer cells and from the infiltration and proliferation of stromal and immune cells from the surrounding tissue and circulation. High-molecular-weight polysaccharides known as hydrogels found in the extracellular matrix (ECM) also add pressure on a tumor. The most well-studied of these hydrogels is hyaluronan; when the polysaccharide absorbs water, it swells, pressing on surrounding cells and structural elements of the tissue. More. (The Scientist, April 1, 2016)

and

May the Force be with you

The dissection of how cells sense and propagate physical forces is leading to exciting new tools and discoveries in mechanobiology and mechanomedicine.

Of course, mechanical properties and forces aren’t just important in disease, but in health as well. Almost all living cells and tissues exert and experience physical forces that influence biological function. The magnitudes of those forces vary among different cell and tissue types, as do cells’ sensitivities to changes in magnitudes, frequencies, and durations of the forces. Touch, hearing, proprioception, and certain other senses are well-known examples of specialized force sensors. But force detection and sensing are not limited to these special cases; rather, they are shared by all living cells in all tissues and organs. The underlying mechanisms of force generation and detection are not well understood, however, leaving many open questions about force dynamics; the distance over which a force exerts its impact; and how cells convert mechanical signals into biochemical signals and changes in gene expression (The Scientist, February 1, 2017)More.

We may come to understand evolution better if we see what can and can’t happen in physics terms.

See also: Keller: Landscape of biological thought is being “radically reconfigured”

Comments
Key points: Direction selectivity has been widely studied as an example of a complex neural computation. Directional GABA release from starburst amacrine cells (SBACs) is critical for generating directional signals in direction-selective ganglion cells. The mechanisms producing the directional release remain unclear. For SBACs, ordered distribution of sustained and transient bipolar cell inputs along the dendrites is proposed to generate directional GABA release. This study tests whether this hypothesis applies to ON-type SBACs. EPSCs activated at proximal and distal dendritic locations have the same time course. Therefore, the ordered arrangement of inputs from bipolar cells with different kinetic properties cannot be responsible for generating directional GABA release from ON-type SBACs. Abstract: Direction selectivity in the retina relies critically on directionally asymmetric GABA release from the dendritic tips of starburst amacrine cells (SBACs). GABA release from each radially directed dendrite is larger for motion outward from the soma toward the dendritic tips than for motion inwards toward the soma. The biophysical mechanisms generating these directional signals remain controversial. A model based on electron-microscopic reconstructions of the mouse retina proposed that an ordered arrangement of kinetically distinct bipolar cell inputs to ON- and OFF-type SBACs could produce directional GABA release. We tested this prediction by measuring the time course of EPSCs in ON-type SBACs in the mouse retina, activated by proximal and distal light stimulation. Contrary to the prediction, the kinetics of the excitatory inputs were independent of dendritic location. Computer simulations based on 3D reconstructions of SBAC dendrites demonstrated that the response kinetics of distal inputs were not significantly altered by dendritic filtering. These direct physiological measurements, do not support the hypothesis that directional signals in SBACs arise from the ordered arrangement of kinetically distinct bipolar cell inputs. Stincic, Todd & Smith, Robert & Taylor, William. (2016). Time course of EPSCs in ON-type starburst amacrine cells is independent of dendritic location. The Journal of Physiology. 594. . 10.1113/JP272384.Dionisio
January 23, 2018
January
01
Jan
23
23
2018
06:59 PM
6
06
59
PM
PDT
Lewis, Sian. (2017). Sensory processing: The eyes have it. Nature Reviews Neuroscience. 18. . 10.1038/nrn.2017.31.Dionisio
January 23, 2018
January
01
Jan
23
23
2018
05:00 PM
5
05
00
PM
PDT
Dragonflies are superb aerial predators, plucking tiny insect prey from the sky. This ability depends on a visual system that has fascinated scientists for decades, and now one of its visual-target-detecting neurons has been shown to anticipate the image path of prey. Frye, Mark. (2017). Insect Vision: A Neuron that Anticipates an Object’s Path. Current Biology. 27. R1076-R1078. 10.1016/j.cub.2017.08.049.Dionisio
January 23, 2018
January
01
Jan
23
23
2018
04:54 PM
4
04
54
PM
PDT
A recent study shows that retinal direction selectivity influences a subset of cells in primary visual cortex which respond to the optic flow associated with forward motion, while other cortical direction selective cells perform this computation independently. Morrie, Ryan & B. Feller, Marla. (2017). Motion Vision: Cortical Preferences Influenced by Retinal Direction Selectivity. Current Biology. 27. R710-R713. 10.1016/j.cub.2017.05.083.Dionisio
January 23, 2018
January
01
Jan
23
23
2018
04:49 PM
4
04
49
PM
PDT
Detecting visual features in the environment, such as motion direction, is crucial for survival. The circuit mechanisms that give rise to direction selectivity in a major visual center, the superior colliculus (SC), are entirely unknown. We optogenetically isolate the retinal inputs that individual direction-selective SC neurons receive and find that they are already selective as a result of precisely converging inputs from similarly tuned retinal ganglion cells. The direction-selective retinal input is linearly amplified by intracollicular circuits without changing its preferred direction or level of selectivity. Finally, using two-photon calcium imaging, we show that SC direction selectivity is dramatically reduced in transgenic mice that have decreased retinal selectivity. Together, our studies demonstrate a retinal origin of direction selectivity in the SC and reveal a central visual deficit as a consequence of altered feature selectivity in the retina. Shi, Xuefeng & Barchini, Jad & Acaron Ledesma, Hector & Koren, David & Jin, Yanjiao & Liu, Xiaorong & Wei, Wei & Cang, Jianhua. (2017). Retinal Origin of Direction Selectivity in the Superior Colliculus. Nature Neuroscience. 20. . 10.1038/nn.4498.Dionisio
January 23, 2018
January
01
Jan
23
23
2018
04:36 PM
4
04
36
PM
PDT
The circuit mechanisms that give rise to direction selectivity in the retina have been studied extensively but how direction selectivity is established in retinorecipient areas of the brain is less well understood. Using functional imaging in larval zebrafish we examine how the direction of motion is encoded by populations of neurons at three layers of the optic tectum; retinal ganglion cell axons (RGCs), a layer of superficial inhibitory interneurons (SINs), and periventricular neurons (PVNs), which constitute the majority of neurons in the tectum. We show that the representation of motion direction is transformed at each layer. At the level of RGCs and SINs the direction of motion is encoded by three direction-selective (DS) subtypes tuned to upward, downward, and caudal-to-rostral motion. However, the tuning of SINs is significantly narrower and this leads to a conspicuous gap in the representation of motion in the rostral-to-caudal direction at the level of SINs. Consistent with previous findings we demonstrate that, at the level of PVNs the direction of motion is encoded by four DS cell types which include an additional DS PVN cell type tuned to rostral-to-caudal motion. Strikingly, the tuning profile of this emergent cell type overlaps with the gap in the representation of rostral-to-caudal motion at the level of SINs. Using our functional imaging data we constructed a simple computational model that demonstrates how the emergent population of PVNs is generated by the interactions of cells at each layer of the tectal network. The model predicts that PVNs tuned to rostral-to-caudal motion can be generated via convergence of DS RGCs tuned to upward and downward motion and feedforward tuned inhibition via SINs which suppresses responses to non-preferred directions. Thus, by reshaping directional tuning that is inherited from the retina inhibitory inputs from SINs can generate a novel subtype of DS PVN and in so doing enhance the encoding of directional stimuli. Abbas, Fatima & A. Triplett, Marcus & J. Goodhill, Geoffrey & Meyer, Martin. (2017). A Three-Layer Network Model of Direction Selective Circuits in the Optic Tectum. Frontiers in Neural Circuits. 11. 88. 10.3389/fncir.2017.00088.Dionisio
January 23, 2018
January
01
Jan
23
23
2018
03:40 PM
3
03
40
PM
PDT
Images projected onto the retina of an animal eye are rarely still. Instead, they usually contain motion signals originating either from moving objects or from retinal slip caused by self-motion. Accordingly, motion signals tell the animal in which direction a predator, prey, or the animal itself is moving. At the neural level, visual motion detection has been proposed to extract directional information by a delay-and-compare mechanism, representing a classic example of neural computation. Neurons responding selectively to motion in one but not in the other direction have been identified in many systems, most prominently in the mammalian retina and the fly optic lobe. Technological advances have now allowed researchers to characterize these neurons' upstream circuits in exquisite detail. Focusing on these upstream circuits, we review and compare recent progress in understanding the mechanisms that generate direction selectivity in the early visual system of mammals and flies. Mauss, Alex & Vlasits, Anna & Borst, Alexander & Feller, Marla. (2017). Visual Circuits for Direction Selectivity. Annual review of neuroscience. 40. . 10.1146/annurev-neuro-072116-031335. Expected final online publication date for the Annual Review of Neuroscience Volume 40 is July 8, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.Dionisio
January 23, 2018
January
01
Jan
23
23
2018
03:30 PM
3
03
30
PM
PDT
Although much is known about the regenerative capacity of retinal ganglion cells, very significant barriers remain in our ability to restore visual function following traumatic injury or disease-induced degeneration. Here we summarize our current understanding of the factors regulating axon guidance and target engagement in regenerating axons, and review the state of the field of neural regeneration, focusing on the visual system and highlighting studies using other model systems that can inform analysis of visual system regeneration. This overview is motivated by a Society for Neuroscience Satellite meeting, “Reconnecting Neurons in the Visual System,” held in October 2015 sponsored by the National Eye Institute as part of their “Audacious Goals Initiative” and co-organized by Carol Mason (Columbia University) and Michael Crair (Yale University). The collective wisdom of the conference participants pointed to important gaps in our knowledge and barriers to progress in promoting the restoration of visual system function. This article is thus a summary of our existing understanding of visual system regeneration and provides a blueprint for future progress in the field. C. Crair, Michael & A. Mason, Carol. (2016). Reconnecting Eye to Brain. Journal of Neuroscience. 36. 10707-10722. 10.1523/JNEUROSCI.1711-16.2016.Dionisio
January 23, 2018
January
01
Jan
23
23
2018
01:42 PM
1
01
42
PM
PDT
The roles of glia and polyamines (PA) in brain function and dysfunction are highlighted in this review. We emphasize that PA accumulation preferentially in glia, but not in neurons, is clearly evolutionarily determined; it is found throughout the brain, retina, peripheral nervous system, and in glial-neuronal co-cultures of multiple species, including man. This phenomenon raises key questions: (i) What are the mechanisms that underlie such uneven distribution, accumulation and release from glia? (ii) What are the consequences of PA fluxes within the brain on neuronal function? (iii) What are the roles of PAs in brain disorders and diseases? This review includes suggestions on the roles of PAs, such as putrescine (PT), spermidine (SPD), spermine (SPM) and their derivatives as novel glio-transmitters in brain since PA affect many neuronal and glial receptors, channels and transporters. Polyamines hitherto have been neglected, although it is evident that these molecules are key elements for normal brain function and their metabolic disorders, apparently, cause the development of many pathological syndromes and diseases. The study of endogenous PA allows one to put forward the basic principles of scientific research on glio-neuronal interactions and clinical therapies, which are based on the exclusivity of glial cells in terms of accumulation of PA and PA-dependent functions. Skatchkov, Serguei & Antonov, Sergei & Eaton, Misty. (2016). Glia and glial polyamines. Role in brain function in health and disease. Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology. 10. 73-98. 10.1134/S1990747816010116.Dionisio
January 23, 2018
January
01
Jan
23
23
2018
01:28 PM
1
01
28
PM
PDT
The article deals with problems of color perception under LED lighting. We revealed that inadequate perception of a signal color by a driver led to greater risks of transport accidents. We reviewed both Jung-Helmholtz three-color hypothesis and a modern one based on fiber-optical approach to functioning of "Mueller cells and cones" system. We made an attempt to explain a number of effects related to visibility curves and time delays when defining color of light signals. Our research on assessing influence exerted by LED lighting on functional state and working capacity of railway workers during which we applied occupational selection techniques revealed negative changes. We proved there was a decrease in functional resistance to color sense between red and green signals as well as longer response time for complicated sight-motor reaction and significant decrease in readiness to emergency actions (resistance to monotony) in examined individuals. The article also contains data on time peculiarities which are characteristic for defining signals color in relation to red signal (650 nm). We showed that when red color LEDs with wave length much shorter than 650 nm were used in signaling devices it caused risks of inadequate color detection, longer reaction to inhibiting signals, and greater possibility of transport accidents and negative events in everyday life. These peculiarities should be taken into account when designing traffic lights and other signaling devices which provide transport safety. We also proved that signaling traffic lights for transport systems should be designed allowing for physiology of color perception by a human visual analyzer; application of LEDs with wave length shorter than 650 nm should be absolutely excluded Kaptsov, V.A. & Deinego, V.N.. (2017). Health risks occurring when color is percepted under led lighting. Health Risk Analysis. 16-25. 10.21668/health.risk/2017.2.02.eng.Dionisio
January 23, 2018
January
01
Jan
23
23
2018
01:19 PM
1
01
19
PM
PDT
We studied intermediate filaments (IFs) in the retina of the Pied flycatcher (Ficedula hypoleuca) in the foveolar zone. Single IFs span Muller cells (MC) lengthwise; cylindrical bundles of IFs (IFBs) appear inside the cone inner segment (CIS) at the outer limiting membrane (OLM) level. IFBs adjoin the cone cytoplasmatic membrane, following lengthwise regularly spaced, forming a skeleton of the CIS, located above the OLM. IFBs follow along the cone outer segment (COS), with single IFs separating from the IFB, touching and entering in-between the light-sensitive disks of the cone membrane. We propose a mechanism of exciton transfer from the inner retinal surface to the visual pigments in the photoreceptor cells. This includes excitation transfer in donor-acceptor systems, from the IF donors to the rhodopsin acceptors, with theoretic efficiency over 80%. This explains high image contrast in fovea and foveola in daylight, while the classical mechanism that describes M\"uller cells as optical lightguides operates in night vision, with loss of resolution traded for sensitivity. Our theory receives strong confirmation in morphology and function of the cones and pigment cells. In daylight the lateral surface of the photosensor disks is blocked from the (scattered or oblique) light by the pigment cells. Thus the light energy can only get to the cone via intermediate filaments that absorb photons in the Muller cell endfeet and conduct excitons to the cone. Thus, the disks are consumed at their lateral surfaces, moving to the apex of the cone, with new disks produced below. An alternative hypothesis of direct light passing through the cone with its organelles and hitting the lowest disk contradicts morphological evidence, as thus all of the other disks would have no useful function in daylight vision. Zueva, Lidia & Golubeva, Tatiana & Korneeva, Elena & Inyushin, Mikhail & Khmelinskii, Igor & Makarov, Vladimir. (2017). Mechanism of light energy transport in the avian retina. .Dionisio
January 23, 2018
January
01
Jan
23
23
2018
01:09 PM
1
01
09
PM
PDT
Presently we continue our studies of the quantum mechanism of light energy transmission in the form of excitons by axisymmetric nanostructures with electrically conductive walls. Using our theoretical model, we analyzed the light energy transmission by biopolymers forming optical channels within retinal Müller cells. There are specialized intermediate filaments (IF) 10–18 nm in diameter, built of electrically conductive polypeptides. Presently, we analyzed the spectral selectivity of these nanostructures. We found that their transmission spectrum depends on their diameter and wall thickness. We also considered the classical approach, comparing the results with those predicted by the quantum mechanism. We performed experimental measurements on model quantum waveguides, made of rectangular nanometer-thick chromium (Cr) tracks. The optical spectrum of such waveguides varied with their thickness. We compared the experimental absorption/transmission spectra with those predicted by our model, with good agreement between the two. We report that the observed spectra may be explained by the same mechanisms as operating in metal nanolayers. Both the models and the experiment show that Cr nanotracks have high light transmission efficiency in a narrow spectral range, with the spectral maximum dependent on the layer thickness. Therefore, a set of intermediate filaments with different geometries may provide light transmission over the entire visible spectrum with a very high (~ 90%) efficiency. Thus, we believe that high contrast and visual resolution in daylight are provided by the quantum mechanism of energy transfer in the form of excitons, whereas the ultimate retinal sensitivity of the night vision is provided by the classical mechanism of photons transmitted by the Müller cell light-guides. Khmelinskii, Igor & Golubeva, Tatiana & Korneeva, Elena & Inyushin, Mikhail & Zueva, Lidia & Makarov, Vladimir. (2017). Spectral selectivity model for light transmission by the intermediate filaments in Müller cells. Journal of Photochemistry and Photobiology B: Biology. 173. . 10.1016/j.jphotobiol.2017.06.001.Dionisio
January 23, 2018
January
01
Jan
23
23
2018
01:02 PM
1
01
02
PM
PDT
Visually guided behaviour at its sensitivity limit relies on single-photon responses originating in a small number of rod photoreceptors. For decades, researchers have debated the neural mechanisms and noise sources that underlie this striking sensitivity. To address this question, we need to understand the constraints arising from the retinal output signals provided by distinct retinal ganglion cell types. It has recently been shown in the primate retina that On and Off parasol ganglion cells, the cell types likely to underlie light detection at the absolute visual threshold, differ fundamentally not only in response polarity, but also in the way they handle single-photon responses originating in rods. The On pathway provides the brain with a thresholded, low-noise readout and the Off pathway with a noisy, linear readout. We outline the mechanistic basis of these different coding strategies and analyse their implications for detecting the weakest light signals. We show that high-fidelity, nonlinear signal processing in the On pathway comes with costs: more single-photon responses are lost and their propagation is delayed compared with the Off pathway. On the other hand, the responses of On ganglion cells allow better intensity discrimination compared with the Off ganglion cell responses near visual threshold. This article is part of the themed issue ?Vision in dim light?. Takeshita, Daisuke & Smeds, Lina & Ala-Laurila, Petri. (2017). Processing of single-photon responses in the mammalian On and Off retinal pathways at the sensitivity limit of vision. Philosophical Transactions of the Royal Society B: Biological Sciences. 372. 20160073. 10.1098/rstb.2016.0073.Dionisio
January 23, 2018
January
01
Jan
23
23
2018
12:16 PM
12
12
16
PM
PDT
Cellular luminescence is the emission of photons by living cells due to various biophysical and biochemical processes, mostly associated with cellular metabolism. In this review paper we summarize today's understanding of four luminescence-dependent phenomena in the eye, i.e., phosphenes, retinal discrete dark noise, negative afterimages and the development of retinogeniculate projections in the brain. We review the phenomena above in the context of knowledge gained from experimental and theoretical works. Finally we discuss this knowledge in terms of its physiological significance. Salari, Vahid & Scholkmann, Felix & Vimal, Ram Lakhan Pandey & Csaszar-Nagy, Noemi & Aslani, Mehdi & Bokkon, Istvan. (2017). Phosphenes, retinal discrete dark noise, negative afterimages and retinogeniculate projection: A review of a new explanatory framework based on endogenous ocular luminescence. Progress in Retinal and Eye Research. 60. . 10.1016/j.preteyeres.2017.07.001.Dionisio
January 23, 2018
January
01
Jan
23
23
2018
11:50 AM
11
11
50
AM
PDT
Analysis of everyday human gaze behaviour has significant potential for ubiquitous computing, as evidenced by a large body of work in gaze-based human-computer interaction, attentive user interfaces, and eye-based user modelling. However, current mobile eye trackers are still obtrusive, which not only makes them uncomfortable to wear and socially unacceptable in daily life, but also prevents them from being widely adopted in the social and behavioural sciences. To address these challenges we present InvisibleEye, a novel approach for mobile eye tracking that uses millimetre-size RGB cameras that can be fully embedded into normal glasses frames. To compensate for the cameras’ low image resolution of only a few pixels, our approach uses multiple cameras to capture different views of the eye, as well as learning-based gaze estimation to directly regress from eye images to gaze directions. We prototypically implement our system and characterise its performance on three large-scale, increasingly realistic, and thus challenging datasets: 1) eye images synthesised using a recent computer graphics eye region model, 2) real eye images recorded of 17 participants under controlled lighting, and 3) eye images recorded of four participants over the course of four recording sessions in a mobile setting. We show that InvisibleEye achieves a top person-specific gaze estimation accuracy of 1.79° using four cameras with a resolution of only 5 × 5 pixels. Our evaluations not only demonstrate the feasibility of this novel approach but, more importantly, underline its significant potential for finally realising the vision of invisible mobile eye tracking and pervasive attentive user interfaces. Tonsen, Marc & Steil, Julian & Sugano, Yusuke & Bulling, Andreas. (2017). InvisibleEye: Mobile Eye Tracking Using Multiple Low-Resolution Cameras and Learning-Based Gaze Estimation. Proceedings of the ACM on Interactive, Mobile, Wearable and Ubiquitous Technologies. 1. 1-21. 10.1145/3130971.Dionisio
January 23, 2018
January
01
Jan
23
23
2018
11:41 AM
11
11
41
AM
PDT
Eye and gaze movements play an essential role in identifying individuals' emotional states, cognitive activities, interests, and attention among other behavioral traits. Besides, they are natural, fast, and implicitly reflect the targets of interest, which makes them a highly valuable input modality in human-computer interfaces. Therefore, tracking gaze movements, in other words, eye tracking is of great interest to a large number of disciplines, including human behaviour research, neuroscience, medicine, and human-computer interaction. Tracking gaze movements accurately is a challenging task, especially under unconstrained conditions. Over the last two decades, significant advances have been made in improving the gaze estimation accuracy. However, these improvements have been achieved mostly under controlled settings. Meanwhile, several concerns have arisen, such as the complexity, inflexibility and cost of the setups, increased user effort, and high sensitivity to varying real-world conditions. Despite various attempts and promising enhancements, existing eye tracking systems are still inadequate to overcome most of these concerns, which prevent them from being widely used. In this thesis, we revisit these concerns and introduce a novel multi-camera eye tracking framework. The proposed framework achieves a high estimation accuracy while requiring a minimal user effort and a non-intrusive flexible setup. In addition, it provides improved robustness to large head movements, illumination changes, use of eye wear, and eye type variations across users. We develop a novel real-time gaze estimation framework based on adaptive fusion of multiple single-camera systems, in which the gaze estimation relies on projective geometry. Besides, to ease the user calibration procedure, we investigate several methods to model the subject-specific estimation bias, and consequently, propose a novel approach based on weighted regularized least squares regression. The proposed method provides a better calibration modeling than state-of-the-art methods, particularly when using low-resolution and limited calibration data. Being able to operate with low-resolution data also enables to utilize a large field-of-view setup, so that large head movements are allowed. To address aforementioned robustness concerns, we propose to leverage multiple eye appearances simultaneously acquired from various views. In comparison with conventional single view approach, the main benefit of our approach is to more reliably detect gaze features under challenging conditions, especially when they are obstructed due to large head pose or movements, or eye glasses effects. We further propose an adaptive fusion mechanism to effectively combine the gaze outputs obtained from multi-view appearances. To this effect, our mechanism firstly determines the estimation reliability of each gaze output and then performs a reliability-based weighted fusion to compute the overall point of regard. In addition, to address illumination and eye type robustness, the setup is built upon active illumination and robust feature detection methods are developed. The proposed framework and methods are validated through extensive simulations and user experiments featuring 20 subjects. The results demonstrate that our framework provides not only a significant improvement in gaze estimation accuracy but also a notable robustness to real-world conditions, making it suitable for a large spectrum of applications. Arar, Nuri Murat. (2017). Robust Eye Tracking Based on Adaptive Fusion of Multiple Cameras. . 10.5075/epfl-thesis-7933.Dionisio
January 23, 2018
January
01
Jan
23
23
2018
11:29 AM
11
11
29
AM
PDT
The formation of skeletal muscle during embryogenesis involves the commitment of mesodermal progenitors to the myogenic lineage and their fusion to form fibers followed by the expression of muscle structural genes [...] Our demonstrations reveal two additional functions for CF2 not yet reported. First, CF2, is involved in the Mef2 transcriptional regulation. KSecond, CF2 acts at two closely related levels: contributing to the control of fiber size and to the number of nuclei that every fiber will have during embryo muscle differentiation.
CF2 transcription factor is involved in the regulation of Mef2 RNA levels, nuclei number and muscle fiber size Juan J. Arredondo,#* Jorge Vivar,# Sara Laine-Menéndez, Leticia Martínez-Morentin, and Margarita Cervera PLoS One. 2017; 12(6): e0179194. doi: 10.1371/journal.pone.0179194 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472297/pdf/pone.0179194.pdf
The known -not the unknown- clearly points to complex functionally specified informational complexityDionisio
January 22, 2018
January
01
Jan
22
22
2018
06:23 PM
6
06
23
PM
PDT
Building and maintaining muscles is a crucial aspect for the fitness of most metazoan organisms. The proper differentiation and maintenance of myofibers is fundamental to a functional musculature. [...] Mib2 plays an additional important role in the development of adult thorax muscles, particularly in maintaining the larval templates for the dorsal longitudinal indirect flight muscles during metamorphosis. [...] a connection between Mib2 and Notch signaling during flight muscle development remains an interesting possibility that needs to be addressed in future experiments. The identity of the critical Mib2 targets during DLM formation remains to be identified. In this regard, our novel viable hypomorphic alleles could serve as excellent tools for future genetic or proteomic approaches.
Identification of the essential protein domains for Mib2 function during the development of the Drosophila larval musculature and adult flight muscles. Domsch K1, Acs A1, Obermeier C1, Nguyen HT1, Reim I1. PLoS One. 2017 Mar 10;12(3):e0173733. doi: 10.1371/journal.pone.0173733. eCollection 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345843/pdf/pone.0173733.pdf
The known -not the unknown- clearly points to complex functionally specified informational complexityDionisio
January 22, 2018
January
01
Jan
22
22
2018
04:25 PM
4
04
25
PM
PDT
[...] a critical role for macrophage-derived ECM may be more ubiquitous than previously recognized. It is unclear why embryonic BM components like Col IV require local delivery by hemocytes, while in larvae they are thought to diffuse from the fat body [...] [...] it is unclear whether hemocytes associated with the ovary plaster Col IV in a manner similar to embryonic hemocytes or shed soluble Col IV similarly to the larval fat body [...] [...] there are differences between the mechanisms of de novo BM formation in the embryo versus homeostatic mechanisms involved in BM growth [...] [...] specific hemocyte-dependent mechanism of delivery during de novo BM formation.
A Moving Source of Matrix Components Is Essential for De Novo Basement Membrane Formation. Matsubayashi Y1, Louani A2, Dragu A2, Sánchez-Sánchez BJ2, Serna-Morales E2, Yolland L2, Gyoergy A3, Vizcay G4, Fleck RA4, Heddleston JM5, Chew TL5, Siekhaus DE3, Stramer BM6. Curr Biol. 2017 Nov 20;27(22):3526-3534.e4. doi: 10.1016/j.cub.2017.10.001. Epub 2017 Nov 9.
The known -not the unknown- clearly points to complex functionally specified informational complexityDionisio
January 22, 2018
January
01
Jan
22
22
2018
01:39 PM
1
01
39
PM
PDT
a critical role for macrophage-derived ECM may be more ubiquitous than previously recognized. A Moving Source of Matrix Components Is Essential for De Novo Basement Membrane Formation. Matsubayashi Y1, Louani A2, Dragu A2, Sánchez-Sánchez BJ2, Serna-Morales E2, Yolland L2, Gyoergy A3, Vizcay G4, Fleck RA4, Heddleston JM5, Chew TL5, Siekhaus DE3, Stramer BM6. Curr Biol. 2017 Nov 20;27(22):3526-3534.e4. doi: 10.1016/j.cub.2017.10.001. Epub 2017 Nov 9.Dionisio
January 22, 2018
January
01
Jan
22
22
2018
07:01 AM
7
07
01
AM
PDT
Hox genes encode a family of transcription factors responsible for the establishment of the animal body plan. Their organisation in genomic clusters is conserved during evolution and is instrumental in defining the domain of activity of each gene in the embryo: the place and time of Hox gene expression is dictated by the position of each gene within the cluster. A unique set of Hox genes is active at each axial level along the embryonic anterior to posterior axis. These diverse complements of Hox proteins determine morphological identities by controlling the transcription of specific target genes. Changes in Hox genes number, expression and function likely participated in morphological diversification during animal evolution. Lufkin, Thomas. (2005). Hox Genes: Embryonic Development. . 10.1038/npg.els.0005046. https://www.researchgate.net/profile/Thomas_Lufkin/publication/230302351_Hox_Genes_Embryonic_Development/links/0912f50d28284341e8000000/Hox-Genes-Embryonic-Development.pdf 13 yo paperDionisio
January 21, 2018
January
01
Jan
21
21
2018
09:02 AM
9
09
02
AM
PDT
The occurrence of spliceosomal introns in eukaryotic genomes is highly diverse and ranges from few introns in an organism to multiple introns per gene. Introns vary with respect to their lengths, strengths of splicing signals, and position in resident genes. Higher intronic density and diversity in genetically complex organisms relies on increased efficiency and accuracy of spliceosomes for pre-mRNA splicing. Since intron diversity is critical for functions in RNA stability, regulation of gene expression and alternative splicing, RNA-binding proteins, spliceosomal regulatory factors and post-translational modifications of splicing factors ought to make the splicing process intron-specific. We recently reported function and regulation of a ubiquitin fold harboring splicing regulator, Sde2, which following activation by ubiquitin-specific proteases facilitates excision of selected introns from a subset of multi-intronic genes in Schizosaccharomyces pombe (Thakran et al. EMBO J, https://doi.org/10.15252/embj.201796751, 2017). By reviewing our findings with understandings of intron functions and regulated splicing processes, we propose possible functions and mechanism of intron-specific pre-mRNA splicing and suggest that this process is crucial to highlight importance of introns in eukaryotic genomes. Intron specificity in pre-mRNA splicing. Mishra, Shravan Kumar & Thakran, Poonam. (2018). Current Genetics. . 10.1007/s00294-017-0802-8.Dionisio
January 21, 2018
January
01
Jan
21
21
2018
06:13 AM
6
06
13
AM
PDT
Transcription is a source of genetic instability that can notably result from the formation of genotoxic DNA:RNA hybrids, or R-loops, between the nascent mRNA and its template. Here we report an unexpected function for introns in counteracting R-loop accumulation in eukaryotic genomes. Deletion of endogenous introns increases R-loop formation, while insertion of an intron into an intronless gene suppresses R-loop accumulation and its deleterious impact on transcription and recombination in yeast. Recruitment of the spliceosome onto the mRNA, but not splicing per se, is shown to be critical to attenuate R-loop formation and transcription-associated genetic instability. Genome-wide analyses in a number of distant species differing in their intron content, including human, further revealed that intron-containing genes and the intron-richest genomes are best protected against R-loop accumulation and subsequent genetic instability. Our results thereby provide a possible rationale for the conservation of introns throughout the eukaryotic lineage. Introns Protect Eukaryotic Genomes from Transcription-Associated Genetic Instability. Bonnet, Amandine & Grosso, Ana & El Kaoutari, Abdessamad & Coleno, Emeline & Presle, Adrien & C. Sridhara, Sreerama & Janbon, Guilhem & Géli, Vincent & de Almeida, Sérgio & Palancade, Benoît. (2017). Molecular Cell. in press. . 10.1016/j.molcel.2017.07.002.Dionisio
January 21, 2018
January
01
Jan
21
21
2018
06:10 AM
6
06
10
AM
PDT
Reproductive aging is characterized by a marked decline in oocyte quality that contributes to infertility, miscarriages, and birth defects. This decline is multifactorial, and the underlying mechanisms are under active investigation. Here, we performed RNA-Seq on individual growing follicles from reproductively young and old mice to identify age-dependent functions in oocytes. This unbiased approach revealed genes involved in cellular processes known to change with age, including mitochondrial function and meiotic chromosome segregation, but also uncovered previously unappreciated categories of genes related to proteostasis and organelles required for protein metabolism. We further validated our RNA-Seq data by comparing nucleolar structure and function in oocytes from reproductively young and old mice, as this organelle is central for protein production. We examined key nucleolar markers, including upstream binding transcription factor (UBTF), an RNA polymerase I cofactor, and fibrillarin, an rRNA methyltransferase. In oocytes from mice of advanced reproductive age, UBTF was primarily expressed in giant fibrillar centers (GFCs), structures associated with high levels of rDNA transcription, and fibrillarin expression was increased ~2-fold. At the ultrastructural level, oocyte nucleoli from reproductively old mice had correspondingly more prominent fibrillar centers and dense fibrillar centers relative to young controls and more ribosomes were found in the cytoplasm. Taken together, our findings are significant because the growing oocyte is one of the most translationally active cells in the body and must accumulate high-quality maternally derived proteins to support subsequent embryo development. Thus, perturbations in protein metabolism are likely to have a profound impact on gamete health. E. Duncan, Francesca & Jasti, Susmita & Paulson, Ariel & M. Kelsh, John & Fegley, Barbara & L. Gerton, Jennifer. (2017). Age-associated dysregulation of protein metabolism in the mammalian oocyte. Aging Cell. 16. . 10.1111/acel.12676. https://www.researchgate.net/publication/320308458_Age-associated_dysregulation_of_protein_metabolism_in_the_mammalian_oocyte/fulltext/59dd081e45851561891382a4/320308458_Age-associated_dysregulation_of_protein_metabolism_in_the_mammalian_oocyte.pdfDionisio
January 20, 2018
January
01
Jan
20
20
2018
05:37 AM
5
05
37
AM
PDT
Aging is a ubiquitous complex process characterized by tissue degeneration and loss of cellular fitness. Genome instability (GIN) has long been implicated as a main causal factor in aging. The most severe form of genomic instability is whole chromosome instability (W-CIN), a state where dysfunction in chromosome segregation leads to whole chromosomes gains and losses. Aneuploidy is commonly linked to pathological states. It is a hallmark of spontaneous abortions and birth defects and it is observed virtually in every human tumor. There is mounting evidence that W-CIN increases with age, with the underlying hypothesis that some of the age-related loss of fitness phenotypes may be the result of W-CIN. Methodologically, the detection of stochastic W-CIN during the aging process poses unique challenges: aneuploid cells are scattered among diploid cells and, contrary to the cancer genome where aneuploidy is present in the background of massive ploidy changes, the number of aneuploid chromosome per cells is usually low (few per cell). Aging-associated aneuploidy is also largely stochastic or with limited clonal expansion. Therefore analysis at the single-cell level and the examination of a large number of cells is necessary. Here we describe a modification of the standard fluorescent in situ hybridization (FISH) protocol adapted for the detection of low-frequency mosaic aneuploidy in interphase cells isolated from the adult brain or within frozen tissue sections. This approach represents a straightforward method for the single-cell analysis of W-CIN in mammalian cells. It is based on the combination of four probes mapping to two different chromosomes and analysis of interphase cells, highly reducing false positives and enabling studying W-CIN also in post-mitotic tissues. A. Andriani, Grasiella & Montagna, Cristina. (2017). FISH Analysis of Aging-Associated Aneuploidy in Neurons and Nonneuronal Brain Cells. Neuromethods. 271-298. 10.1007/978-1-4939-7280-7_14. https://www.researchgate.net/profile/Cristina_Montagna4/publication/319639553_FISH_Analysis_of_Aging-Associated_Aneuploidy_in_Neurons_and_Nonneuronal_Brain_Cells/links/5a0b18aaaca2721a23f9a443/FISH-Analysis-of-Aging-Associated-Aneuploidy-in-Neurons-and-Nonneuronal-Brain-Cells.pdfDionisio
January 20, 2018
January
01
Jan
20
20
2018
05:32 AM
5
05
32
AM
PDT
A long standing axiom in the field of teratology states that the teratogenic period, when most birth defects are produced, occurs during the third to eighth weeks of development post-fertilization. Any insults prior to this time are thought to result in a slowing of embryonic growth from which the conceptus recovers or death of the embryo followed by spontaneous abortion. However, new insights into embryonic development during the first two weeks, including formation of the anterior-posterior, dorsal-ventral, and left-right axes, suggests that signaling pathways regulating these processes are prime targets for genetic and toxic insults. Establishment of the left-right (laterality) axis is particularly sensitive to disruption at very early stages of development and these perturbations result in a wide variety of congenital malformations, especially heart defects. Thus, the time for teratogenic insults resulting in birth defects should be reset to include the first two weeks of development. W. Sadler, Thomas. (2017). Establishing the Embryonic Axes: Prime Time for Teratogenic Insults. Journal of Cardiovascular Development and Disease. 4. 15. 10.3390/jcdd4030015. http://www.mdpi.com/2308-3425/4/3/15/pdfDionisio
January 20, 2018
January
01
Jan
20
20
2018
04:47 AM
4
04
47
AM
PDT
A societal preference of delaying maternal age at first childbirth has increased reliance on assisted reproductive technologies/therapies (ART) to conceive a child. Oocytes that have undergone physiologic aging (?35 years for humans) are now commonly used for ART, yet evidence is building that suboptimal reproductive environments associated with aging negatively affect oocyte competence and embryo development – although the mechanisms underlying these relationship are not yet well understood. Epigenetic programming of the oocyte occurs during its growth within a follicle, so the ovarian stimulation protocols that administer exogenous hormones, as part of the first step for all ART procedures, may prevent the gamete from establishing an appropriate epigenetic state. Therefore, understanding how oocyte age versus physiologic age independently and synergistically affect the epigenetic programming of these gametes, and how this may affect their developmental competence, are crucial to improved ART outcomes. Here, we review studies that measured the developmental outcomes affected by superovulation and aging, focusing on how the epigenome (i.e., global and imprinted DNA methylation, histone modifications, and epigenetic modifiers) of gametes and embryos acquired from females undergoing physiologic aging and exogenous ovarian stimulation are affected. This article is protected by copyright. All rights reserved Lynn Marshall, Kira & Melissa Rivera, Rocío. (2017). The effects of superovulation and reproductive aging on the epigenome of the oocyte and embryo: Superovulation and aging affect the epigenome. Molecular Reproduction and Development. . 10.1002/mrd.22951. Had we remained in Eden, none of this would have been an issue.Dionisio
January 20, 2018
January
01
Jan
20
20
2018
04:37 AM
4
04
37
AM
PDT
Fibrillarin is one of the most important nucleolar proteins that have been shown as essential for life. Fibrillarin localizes primarily at the periphery between fibrillar center and dense fibrillar component as well as in Cajal bodies. In most plants there are at least two different genes for fibrillarin. In Arabidopsis thaliana both genes show high level of expression in transcriptionally active cells. Here, we focus on two important differences between A. thaliana fibrillarins. First and most relevant is the enzymatic activity by AtFib2. The AtFib2 shows a novel ribonuclease activity that is not seen with AtFib1. Second is a difference in the ability to interact with phosphoinositides and phosphatidic acid between both proteins. We also show that the novel ribonuclease activity as well as the phospholipid binding region of fibrillarin is confine to the GAR domain. The ribonuclease activity of fibrillarin reveals in this study represents a new role for this protein in rRNA processing. Rodriguez-Corona, Ulises & Pereira-Santana, Alejandro & Sobol, Margarita & Rodriguez-Zapata, Luis & Hozák, Pavel & Castaño, Enrique. (2017). Novel Ribonuclease Activity Differs between Fibrillarins from Arabidopsis thaliana. Frontiers in Plant Science. 8. . 10.3389/fpls.2017.01878. https://www.researchgate.net/profile/Alejandro_Pereira-Santana/publication/320734165_Novel_Ribonuclease_Activity_Differs_between_Fibrillarins_from_Arabidopsis_thaliana/links/59f89152aca272607e2f570d/Novel-Ribonuclease-Activity-Differs-between-Fibrillarins-from-Arabidopsis-thaliana.pdfDionisio
January 20, 2018
January
01
Jan
20
20
2018
04:27 AM
4
04
27
AM
PDT
RNA-binding ubiquitin ligases (RBULs) have the potential to link RNA-mediated mechanisms to protein ubiquitylation. Despite this, the cellular functions, substrates and interaction partners of most RBULs remain poorly characterized. Affinity purification (AP) combined with quantitative mass spectrometry (MS)-based proteomics is a powerful approach for analyzing protein functions. Mapping the physiological interaction partners of RNA-binding proteins has been hampered by their intrinsic properties, in particular the existence of low-complexity regions, which are prone to engage in non-physiological interactions. Here, we used an adapted AP approach to identify the interaction partners of human RBULs harboring different RNA-binding domains. To increase the likelihood of recovering physiological interactions, we combined control and bait-expressing cells prior to lysis. In this setup, only stable interactions that were originally present in the cell will be identified. We exploit gene function similarity between the bait proteins and their interactors to benchmark our approach in its ability to recover physiological interactions. We reveal that RBULs engage in stable interactions with RNA-binding proteins involved in different steps of RNA metabolism as well as with components of the ubiquitin conjugation machinery and ubiquitin-binding proteins. Our results thus demonstrate their capacity to link posttranscriptional regulation with the ubiquitin system. Hildebrandt, Andrea & Alanis-Lobato, Gregorio & Voigt, Andrea & Zarnack, Kathi & Andrade, Miguel & Beli, Petra & König, Julian. (2017). Interaction profiling of RNA-binding ubiquitin ligases reveals a link between posttranscriptional regulation and the ubiquitin system. Scientific Reports. 7. . 10.1038/s41598-017-16695-6. https://www.researchgate.net/publication/321369667_Interaction_profiling_of_RNA-binding_ubiquitin_ligases_reveals_a_link_between_posttranscriptional_regulation_and_the_ubiquitin_system/fulltext/5a20b6530f7e9b4d1927feb9/321369667_Interaction_profiling_of_RNA-binding_ubiquitin_ligases_reveals_a_link_between_posttranscriptional_regulation_and_the_ubiquitin_system.pdfDionisio
January 20, 2018
January
01
Jan
20
20
2018
04:23 AM
4
04
23
AM
PDT
Background The Midas cichlid species complex (Amphilophus spp.) is widely known among evolutionary biologists as a model system for sympatric speciation and adaptive phenotypic divergence within extremely short periods of time (a few hundred generations). The repeated parallel evolution of adaptive phenotypes in this radiation, combined with their near genetic identity, makes them an excellent model for studying phenotypic diversification. While many ecological and evolutionary studies have been performed on Midas cichlids, the molecular basis of specific phenotypes, particularly adaptations, and their underlying coding and cis-regulatory changes have not yet been studied thoroughly. Results For the first time in any New World cichlid, we use Tol2 transposon-mediated transgenesis in the Midas cichlid (Amphilophus citrinellus). By adapting existing microinjection protocols, we established an effective protocol for transgenesis in Midas cichlids. Embryos were injected with a Tol2 plasmid construct that drives enhanced green fluorescent protein (eGFP) expression under the control of the ubiquitin promoter. The transgene was successfully integrated into the germline, driving strong ubiquitous expression of eGFP in the first transgenic Midas cichlid line. Additionally, we show transient expression of two further transgenic constructs, ubiquitin::tdTomato and mitfa::eGFP. Transgenesis in Midas cichlids will facilitate further investigation of the genetic basis of species-specific traits, many of which are adaptations. Conclusion Transgenesis is a versatile tool not only for studying regulatory elements such as promoters and enhancers, but also for testing gene function through overexpression of allelic gene variants. As such, it is an important first step in establishing the Midas cichlid as a powerful model for studying adaptive coding and non-coding changes in an ecological and evolutionary context. Kratochwil, Claudius & Sefton, Maggie & Liang, Yipeng & Meyer, Axel. (2017). Tol2 transposon-mediated transgenesis in the Midas cichlid (Amphilophus citrinellus) - Towards understanding gene function and regulatory evolution in an ecological model system for rapid phenotypic diversification. BMC Developmental Biology. 17. 15. 10.1186/s12861-017-0157-x. https://www.researchgate.net/profile/Claudius_Kratochwil/publication/321261482_Tol2_transposon-mediated_transgenesis_in_the_Midas_cichlid_Amphilophus_citrinellus_-_Towards_understanding_gene_function_and_regulatory_evolution_in_an_ecological_model_system_for_rapid_phenotypic_div/links/5a1979bda6fdcc50ade812db/Tol2-transposon-mediated-transgenesis-in-the-Midas-cichlid-Amphilophus-citrinellus-Towards-understanding-gene-function-and-regulatory-evolution-in-an-ecological-model-system-for-rapid-phenotypic-div.pdfDionisio
January 19, 2018
January
01
Jan
19
19
2018
05:57 AM
5
05
57
AM
PDT
1 2 3 12

Leave a Reply