Dissapointed with Papers2

Why, on Earth, would you release an upgrade from a popular software, only for a limited number of users because your new, improved, released software supports only the last operative system? Why the people behind Papers released the long-long-long time awaited Papers2 only for Snow Leopard Users?
I was recently reading a post regarding why Mac users still use Leopard instead of Snow Leopard. Lack of time to make the upgrade, the sense of the upgrade being unnecessary, specially considering that you have to pay for the upgrade, and reports about several bugs and incompatibilities, lead users so use Leopard even today. Most of my scientists friends are Leopard users, and also Papers1.x users, and I believe that they are happy. Despite the lack of features awaited for a long time. Even considering that Mendeley is free and always improving. And considering that, for example, Mendeley Lite for iPad is free, in contrast to Papers for iPad (which, by the way, still lacks many features).
But I have been a strong supporter of Papers. I truly believed that, somehow, old Papers1.x users were going to be awarded because of their loyalty. But the upgrade price seems to be a barrier for many, specially for students (and I believe that the new Mac-Student users will turn undoubtedly to Mendeley and Endnote), and to me (and I am pretty sure that for many others too), the need of having Snow Leopard puts another big issue to deal with.
Also, some reports about missing features, bugs and others (see http://support.mekentosj.com/discussions/problems/3118-papers-2-going-back-to-papers-1). The only explanation I found regarding this “hard” decision is:

Unfortunately Papers2 requires 10.6. This was a hard decision, because we know we still have a small percentage of Papers1 users running OS X Leopard 10.5. However, supporting 10.5 had also a lot of technical consequences. In particular, with OS X Lion 10.7 coming soon, we might have had to cut 10.5 support later, which would have been much more difficult to do on paying costumers.

Note of course that your copy of Papers1 will still work the exact same way as it does today on 10.5 for as long as needed.

I believe that the company does not care about loyal, old users of Papers. They say the percentage of Leopard users is small. In my experience, this percentage is pretty close to 100% (maybe because I am in a small, less-developed country, I don’t know), but this only decision is enough to me to decide not to upgrade to Papers2, and I recommend to you to do the same.

In the future, I will be featuring new softwares and tools for scientists, to compensate somehow this huge turn-off.


New directions and projects

The last year, and the beginning of 2011, has been full of projects, work and other stuff. All this had me away from the blog. As a scientist, sometimes things get really hard to maintain in a specific way. And the blog is the downfall of all the work that I have been doing lately.

Chapter One. Just… Research

For example, here in Chile, the spring (starting in September) becomes THE season of meetings and events. In october, I had the pleasure to participate in the European Wnt Meeting, held on the Karolinska Institutet, Stockholm. Back at home, I had now the opportunity to attend the 5th meeting of the Latin American Society of Developmental Biology (LASDB), featuring important scientists from all the world. It was an incredible experience, to participate in both events. But, as many of you probably know, you come back from these events with your head full of ideas. Translating those into a planned experiment, testing the conditions and getting results can take a lot of time. And I am still in that process.

Chapter Two. About Advocacy

I proposed to an Association of Researchers in Graduate Level” (sort of translation), an idea to promote science in the people, to reach authorities and to promote science in the media, among other things. This campaign has been difficult to develop. The lack of funding, and contacts outside the science world, makes this advocacy campaign an “impossible” plan. I really admire the strength of the “Science is Vital” initiative. But we are far from that success and resources.

Chapter Three. Related Stuff.

I collaborated with some posts on The Node, the more-than-awesome blog and community around the Development journal. I also published some letters in chilean newspapers, about the state of Science in our country. These media included El Mostrador (the first and most important digital newspaper), letters in La Tercera and El Mercurio (the two most prominent printed newspaper), and others.


It has been interesting. All this work. But I believe that, this year, I will come back to my roots at Astu’s Science Blog. But excluding more discussions regarding Mendeley, Papers and related software. Science life or, more exactly, scientist life, will be my most common topic this year (I hope).

What I have been doing lately

Well… This is my first post written from my iPad. I have been a little dissapeared from the blog lately. The last three months have been crazy: I had to go to an european meeting in Sweden (which means, exactly, to fly from the other end of the world), then back to help in the development of an international course on regeneration, then going to another international meeting, in Chile this time, then back to the lab to planning new experiments and discuss ideas with my PI, adding the comments of other researchers gathered in the two meetings, and writing some stuff for an advocacy project and also writing some post for the outstanding The Node.

After all this work, I am tired. Obviously. It is hard when you don’t see a reward for your efforts. Only a few comments in my posts regarding the “Paper versus Mendeley” battle keep this blog alive; I am pretty sure that, if I send to the trash those posts, the visits will drop to zero. I am also thinking that the advocacy project will fail, mainly becausethe lack of energy of chilean scientists to fight to change the awful scenario for science funding amd science policy. I like to write, but writing without knowing if someone is reading your work is just dissapointing. I have to manage todo all these things in a pretty much demanding lab (my PI has great expectations in his graduate students, and he also likes having his students 24/7 in the lab), and also I have a family life, and doing this stuff implies less time with them. So, I decided to leave the blog unattended for some weeks.

For those of you following the “Papers versus Mendeley” issue, I have news indeed: I wrote about Mendeley for iPad. I could not keep using Mendeley: it crashes, it is slow, downloading one paper at the time from my online account and many other little details pushed me to test Papers for iPad. And it really rocks! I will not make a review of Papers for iPad. Just use it. I believe that the iPad is one of the best news for scientists. To date, I am saving paper because I read papers only on the iPad; I give presentations with the iPad, and many other things too. The only feature missing in iPad (that makes me to not saying that the iPad is perfect for scientists) is the ability to incorporate error bars in charts.

Anyway, I need to sleep now. Best regards.

About Meetings…

I am back in Chile. I went to the European WNT2010 Meeting, held at the Karolinska Institutet, Sweden. It was a very wonderful meeting, specially to me. I don’t have so often the opportunity to go to another far country, and share my results with the authors of the papers I usually read. It is a great time also to learn, the new techniques, theories and trends in the field.

Main entrance to the Karolinska Institutet at Solna, Stockholm, Sweden.

This meeting was full of prominent researchers in the Wnt field. I presented my results from my PhD research Thesis, and it was extremely fantastic to receive the comments and suggestions from experts. And it was really cool to give a talk with my iPad. Actually, I was initially afraid to go with my iPad in the travel. But soon I realized that it was a very good choice. In the airport, I got delayed in a 4-hour delay. Most people were wondering where to plug their computers because of the small battery time they had. But my iPad had 10 hours of battery so I just used it without worries. Also, in some places the WiFi connection was paid, so I used my 3G connection. Wonderful. Once in the meeting, it was very useful to take my iPad in the conferences, take notes, review the maps of Stockholm, and other things. In this travel, I take out most of my iPad. I had an App to review the climate changes, details of my flight, how to get to some places, reviewing some papers…

And giving a presentation with the iPad is very nice. You will have a black screen showing the slide number (as far as I can remember… I was a little nervous), and the keynote presentations displays very well in the big screen. Also, if you forget your laser pointer, you have an option in the iPad: you keep pressed your finger in the screen, and a point very similar to a laser point will show up in the screen. You have to keep pressed your finger, and you can move across the screen to move the pointer.

Now we have another interesting meeting here in Chile: the meeting from the Latin American Society of Developmental Biology (http://www.lasdb2010.com/, if you can review the program). I will be out some time until the “meeting season” ends. Best regards.

iPad in Research 1.0

If you are a scientist doing your PhD, or at the beginning of a postdoctoral position, or if you have a family (and so on) you will find with little time to learn and investigate deeply enough before to make a decision about purchasing an iPad and taking it to the lab. Searching for experiences with iPad’s users in research is a good start. It worked a little for me. And I promised myself to keep people updated about my experience with iPad in research. Useful or useless? Free or Paid’s apps? iWork or DocsToGo?

With some weeks of use, I will give you some personal advice and comments about iPad in research.

iPad in Research: comments and advice.

1. Maybe, the first statement, is the following: iPad will change your life. Absolutely. For the basics, at least. I remember when I went once to a meeting with my old laptop, weighting almost 3 kilograms. It was awful. With the iPad, you will have a light device to check your email, send emails, reading papers, searching Pubmed, reading Nature/Science, reading a manuscript… I find myself lately going with the iPad to bed to read some paper. You will find yourself replacing the heavy laptop with the iPad to check your email, and reading papers. It’s just great for this basics. Your back will be happy when going to meetings.

2. Being said that, the iPad is not suitable to create scientific material. This only point makes the purchase of an iPad not worthwhile if you want to replace your laptop for scientific needs. Here I will tell you 3 key points.

a) It is almost impossible to create a scientific presentation on the go. Even more… It’s almost impossible to carry with you the powerpoint of your PhD defense/presentation without spend hours making conversions and adjustments. The first time I sent a powerpoint presentation to an iPad, the result was awful. The same with keynote presentations. In order to carry a presentation with you, you must insert all the images as PNGs. This is just plain stupid, and the people from Apple really need to fix this. If you are a patient scientist, you can convert and fix all your presentations. But, at this point, Keynote and DocsToGo are made for basic needs only,

b) If that was not enough reason, here is the second big problem. You can’t create charts with error bars! This one is really painful. This means two things, my fellow researcher: you can’t create scientific charts on the go, which will push you back to the laptop to analyze and plot data; and second, you can’t view charts with error bars in Keynote! One of the best things about Keynote for research in Mac is the ability to copy a chart from Numbers, and modifying the size, colors, and other features in Keynote without the need of opening Numbers over and over (I remember trying to change the font size in a chart in Powerpoint, and waiting for Excel to open, closing the window, waiting that the expected change was good enough… with iWork you can forget about that old “Window’s pain”). But with iPad, you will need to export the charts as images (again, PNG format) and inserting them in the presentations, which is a sort of “what’s the point in having iWork if it will function as an office from the 2000 year”.  Apple: you really need to fix this if you want to have the iPad going massively into the laboratories.

c) At this point, the lack of multitasking makes difficult to use iPad for serious scientific work. Also, Apple needs to work on big improvements on Safari for iPad (for example, allowing the download of PDF files -a.k.a. “papers” to us).

3. Nonetheless, the iPad is still very useful to daily needs. I read journals in the iPad (although you can’t save PDF from Safari… your best shot is having a PDF reader with a built-in browser), check my email, and carrying my presentations (I had to fix all of them). Also, if you are a traveller, you will have many apps useful for you.

4. About apps: Many apps are available to scientists. Periodic table of elements, some biological apps, even the “iPathways” (which you can use to read molecular pathways in SBML language) are available. Maybe the most important choice is what software you will use to manage your scientific papers. Before the iPad, I was a strong follower of Papers for Mac. I had many, many, many reasons to choose Papers over Mendeley. But now, I am slowly changing to Mendeley. Why? For many reasons. First, Mendeley (a “lite” version, tough) is free, and Papers exist as a “paid” version only. You will pay for a version that makes almost the same that the free Mendeley, except for highlighting. But, what’s the point on paying for highlight papers if you will not be able to export those annotations and highlights to your Mac?! Besides, what happens if you are a Windows user? In that case Mendeley is your “only” option. I see a near future where people will change to Mendeley. Half of the iPad’s users are Windows users, so they will use Mendeley soon. The other half, the Mac user, will think: “Well… I paid for the desktop version of Papers… Do I have to pay again for the iPad version (a high price, compared to other PDF readers apps with highlighting and annotation features), considering that I can export my entire library to a free account on Mendeley online and having a “lite”, free version of Mendeley?” Of course, this will change as soon as Mendeley releases a paid version (the called “Mendeley Pro“?). Then the real battle will begin. So far, I think Mendeley Lite for iPad covers most of my needs. I have to make a workaround to use it: exporting a custom collection in Papers (which I called “iPad”, jejeje) as a bib file; opening this collection in Mendeley, choosing to sync the PDF files linked to this collection onto my online account, and downloading those PDF onto Mendeley on iPad. But hey, I am already making worst workarounds to carry on my presentations.


As a normal user, I find iPad a life-changing. Really. But, as a scientists, iPad still need some improvements. Being more specific, more suitable Apps are needed to the scientific community. Allowing the creation of scientific charts (with error bars!), more flexibility in Keynote, and multitasking are extremely urgent needs. There is a niche in which companies can still work to gain more money and followers. For example, Papers could release a “lite” version of Papers for iPad, or maybe offering some kind of discount to the desktop users. Paying a total of $57 for the desktop+iPad combo, now with an improved (and improving every day), free Mendeley at $0? I would change now to Papers for iPad with a “lite” version.

The scientific websites should also work on improving accessibility for iPad. For example, journals would release versions for iPad (and tablets) of their magazines. They would gain more subscriptions. There is a lot of potential on iPad in research. I recommend having an iPad for your normal needs, but I hope and wait for improvements in iWork and other Apps.

Papers versus Mendeley: the mobile wars

One of the goals of this blog is to keep you posted with my experiences about Mac in research.

A series of posts regarding bibliographic management have been very read and commented. I am still a big Papers user. I am still believe that Papers for Mac is way better than Mendeley, although I respect so much Mendeley because of its integration with web (and saving papers and reading them everywhere) and the online community and sharing capabilities (and, obviously, because it’s free).

However, the future is here, and mobile devices are staying for long. The launch of iPad opened a new battlefield: which software would come to colonize iPad’s bibliographic management?

And then, finally, I manage to have an iPad. I truly believe that the iPad can be useful for research. We need more time so the apps improve their evident flaws (for example, no error bars in Numbers?). But Papers and Mendeley were right there, ready for one more battle.

The battle seemed unfair from the beginning. Papers allows you to sync pdf files even via WiFi. In Mendeley, you have to upload your pdf files to your online account (time…), and then, back into the iPad, download the papers in Mendeley (more time…). Papers allows you to make annotations and highlighting. Nothing in Mendeley. Again, Papers seemed the winner again, but…

Having paid for the Mac version, I would expect a more affordable iPad version for Papers’s current users. I don’t know if the App Store allows to make such a discount; nonetheless, having paid for the iPad, the case, the iWork suite, and some other necessary stuff, paying for Papers in iPad for now is out of options.

So, I started to use Mendeley (despite that I hate Mendeley… in my iPod touch, Mendeley crashes often). But I am getting used to upload papers in my online account and then downloading them into iPad’s Mendeley. I can’t make annotations, I can’t search in search engines like in Papers but… when some folks have been working hard to keep an App free of charge, and when, in the other side, some folks decide to charge (reasonable, of course) for the iPad version even to current users from the desktop application, well… I remember when I lost my cell phone once. I went to the company’s office, thinking that I should pay for a new cell phone, and then the girl from the company told me that the phone was free of charge, because “to our company, our customers are important and we want to keep you with us for many years”. Scientists don’t make lots of money. In fact, US$15 here in my country are almost 5 times more expensive, if we consider the GDP per capita. I will end sooner or later buying the Papers for iPad, and maybe I will update this post. Until then, I think that, for now, Mendeley won the mobile war because, at the end, if you own an iPad, you will spend lots of money in many apps, cases, keyboards, and stuff, and every cent will count, specially in smaller (poor) countries.

Let’s save Punta de Choros

Chile is in front of one of the most important challenges in the next years: to deal with an increased demand of energy. Naturally, many options are proposed by different “players”. But two big forces are in the final battle. By one hand, one consortium is a big defender of hydroelectric power, installing several dams. In second place, another group is claiming that nuclear energy is the only option for satisfy chile’s demand of energy.

In the meanwhile, many small thermoelectric (gas, oil, or coal) power plants are being installed. One of them is placed near to a region known as “Punta de Choros”. The international audience is not aware of the upcoming damages that this power plant could do to this region. The following video (in spanish and with english subtitles) explain some of the probable damages. It is enough to say that Punta de Choros is an extremely important region for biologists and ecologists. It harbors important species and is a natural Marine reserve.

The big problem here also is that, as in many other issues, Chilean scientists are not being listened at all. Many scientists are claiming that wind energy is the best option for our country: it is clean, affordable for a country with economic stability, suitable to increase the energy’s demands, and also feasible considering the abundance of wind in several places in our country. Enemies state that the costs of wind energy are very high (without serious studies), and that this energy is not suitable. Well… let’s see. The following figure shows the energy produced in our country, in the context of wind energy:

A recent article in Science (Vol. 329, pp. 382-385) also reviews the proposed alternative to thermal and nuclear plants: flooding of valleys and rivers in the Patagonia, losing precious ecosystems and biodiversity. It is very dissapointing to see how chilean authorities don’t want to listen to scientists and engineering, and to see wind energy and other clean energies (such as solar) as a real option.

On individuality, stochasticity and buffering

ResearchBlogging.org One of the most exciting fields opened in the last years is the new understanding of the existence of something that we could call as “biological heterogeneity”. This new field of study is focused in observing and understanding the differences between reactions of a same kind, between cells of a same kind, and ultimately, between members of the same species. Specially, cellular heterogeneity constitutes a major focus of interest among biologists today, because of its implications in development and diseases such as cancer (Altschuler and Wu, 2010).

Blinded by a deterministic view of the world, born with the discovery of the concept of the gene, biologists forgot, by many years, that not all the processes could be entirely specified by instructions encoded as a biological “bit of information”. And so, to study a specific cellular event, for example, the synthesis of an enzyme to produce a chemical reactions, biologists saw the process as a continuous event, in which all the cells started to synthesize the enzyme, at the same rate, leading to a single “state” which could be measured simply by averaging the measure of the enzyme concentration at the same time (Figure 1A). Hence, the particular amount of an enzyme at a specified time, meant that all the cells had the same amount, with small variations that can be represented as standard deviation.

However, by 1957, Novick and Weiner observed unexpected results from the study of the formation of β-galactosidase in the presence of low concentrations of an inducer. The linear growth of the production of the enzyme was unexpected, because it was known that the concentration of the inducer increases with the production of a permease which allowed the transport of the inducer. Novick and Weiner determined that, at low concentrations of the inducer, the population consisted “essentially of individual bacteria that are either making enzyme at full rate or not making it at all”.  Such a rationale implies reconsider the usual thinking in terms of average in biochemical assays: an average can represent two discrete populations in terms of their behavior (Figure 1B).

Figure 1. Heterogeneity in a cellular response can lead to an “average response”, but the cellular population can either consists in cells showing an incremental and graded response (A) or an ON/OFF response (B). In the latter, drawing conclusions from the average can lead to a wrong interpretation of the biological phenomena.

Nowadays, there is a growing number of publications regarding the concepts of “noise”, “heterogeneity”, “stochasticity” and so on. One key difference between “noise” and “heterogeneity” is that heterogeneity is “a property of a cell population, not of individual cells” (S. Huang, 2009), whereas noise can be defined as a change in the distribution of amount of a measurable trait in a non-expected pattern. Depending on the author, a same word can mean similar (but not equal) things, but the key is to recognize the existence of variations between “biological units” (a cell, for example), even when these units have an equivalent genetic background. For example, individual cells derived from a clone can present different levels of expression for a same gene. These differences can have different origins. One example is heterogeneity between the cells. Two cells can respond differentially to a growth factor, due to a differential spacial localization. In the mouse embryo, at the 8-cell stage, starts the zygotic expression of Cdx2, but is has been reported that the initiation of CDX2 expression is not uniform, and this could be due to the specific locations of the blastomeres in the embryo (Zernicka-Goetz et al, 2009). This class of heterogeneity is referred as “extrinsic heterogeneity”, defined as “cell-to-cell variability in a population caused by non-uniform environmental factors that differentially affect individual cells” (S. Huang, 2009).

Opposed to the extrinsic heterogeneity, there is an “intrinsic heterogeneity”, which cannot be ascribed to environmental differences. In this case, the factors inducing heterogeneity are most probable intracellular. The most attractive source of intrinsic heterogeneity is the “noise” in biological processes. Noise is indeed a property of individual cells, and can be “temporal”, when the changes are observed across a time period, and also at the population levels, when the temporal noise in individual cells triggers different “states”.

Probably, the most interesting hypothesis to explain the presence of noise that transcriptional or translational bursts. Measuring single mRNAs (using FISH), it has been observed a particular mRNA can be transcribed in infrequent but potent bursts leading to cell-to-cell variations in mRNA number. A recent work reviews extensive evidence regarding the variations in mRNA/protein synthesis that can lead to noise (Raj and van Oudenaarden, 2008).

Heterogeneity, as a concept, is relevant when biologists select a scientific question and design experiments to answer that question. For example, studying the expression profile of a gene in time. Simply averaging the amount of the specific gene could lead to the wrong conclusion that the entire population produces a specific time, hiding the fact that one part of the population express high levels of the transcript, whereas the other part of the population express low levels, showing an ON/OFF behavior rather that a OFF-low-mid-high levels.

Can noise or heterogeneity at the cell level translate at the organism level? So far, the vast majority of the work has been focused in studying single cells, or characterizing cell-to-cell variability. But let us to make an exercise: if heterogeneity is a common property of cells, how does the organism to develop in such a patterned structure? For example, imagine a theoretical embryo (Figure 2A). This embryo has 32 cells (a 32-cell stage), and all its cells are performing biochemical and genetic processes influenced by extrinsic heterogeneity (such as the case of Cdx2), and intrinsic noise due to transcriptional bursts, chromatin remodeling and so on. As the embryo develops, three options remains: a) the stochasticity influences the development and the embryo grows in a stochastic pattern (Figure 2C); b) the embryo develops in an ordered pattern because, together with the stochasticity, the embryo harbors a system to buffer the noise (Figure 2A); c) the variability between cells makes a final average noise of zero (Figure 2B), as in a sum of two numbers with different sign (-2 + 2).

Figure 2. Control of noise in a theoretical embryo. Assuming the majority of the cells in the embryo display noise in their biological processes, specially transcription/translation, the embryo can buffer this noise by decreasing the influence of the noise through a biochemical network (A). Another possibility is that the noise becomes stabilized by a vectorial sum (B), where opposing effects of noise (for example, one cell express high levels of a ligand and another cell express low levels, leading to a physiological average”). Finally, if noise predominates, the embryo could display an unpredictable development (C).

Since many years, developmental biologists have been studying biochemical pathways with a special relevance to embryonic development. Any biochemical pathway is candidate to impose a buffer to heterogeneity and noise. Please consider that noise in embryo development is highly relevant, because initially everything start with one cell. It has been proposed that a mechanism to control noise is the negative feedback in circuits (Raj and van Oudenaarden, 2008). Fluctuations above and below the average are pushed back in those feedback loops. One classic example of negative feedback is provided by the Wnt pathway, which have a key role in embryonic development. The Wnt pathway comprises a family of secreted ligands, which can be divided into “canonical” ligands that activates the transcription factor β-catenin, and “non canonical” ligands that activate intracellular effectors which act in a β-catenin independent fashion (in a summarized view, because many data demonstrate that such classification is not always precise). In the canonical pathway, Axin2 is a target of the stabilized β-catenin, and acts as a negative regulator of the pathway, providing negative feedback. Theoretical and experimental evidence from the work of Lea Goentoro and Marc Kirschner (Goentoro and Kirschner, 2009) showed that the canonical Wnt pathway displays an interesting behavior: its activity is dictated by the fold-change in β-catenin levels and not to the absolute level of this transcription factor. The authors propose that, in such a system, noise os buffered, because simple variations in gene expression are not able to activate the pathway: it is required a precise threshold of variation in the components to variate the fold-change of β-catenin and, concomitantly, activate the pathway. Parallel work of Lea Goentoro (Goentoro et al, 2009, in the same issue of the Molecular Cell journal) explain how a circuit can provide fold-change detection, giving to a cell an advantage in a “noisy environment”. It is really interesting that many negative regulators of the Wnt pathway are, in fact, target of β-catenin: the pathway activates its own negative regulators, as evidenced by studying the transcriptional response of antagonists of the pathway in HEK293 cells (Gujral and MacBeath, 2010). It remains an open question whether the Wnt pathway can buffer noise and provide homogeneity to the embryo to allow development. Maybe the developmental patterning is encoded precisely in heterogeneity, but since heterogeneity is unpredictable, and since we can predict the development of the embryo, it seems more likely that the embryo display specific responses, in the form of pathways with negative feedback and response to fold-change of key elements (instead of responding to small changes in the amount of these elements), to buffer noise.

Finally, we must consider that not all the noise is a bad thing during development. Two examples show us that the heterogeneity is necessary during development. In the Drosophila eye, the optical units that compose the eye contains photoreceptors, which specification is provided by a stochastic process, where in a specific cell type (R7), the stochastic expression of the spineless gene dictates the Rh4 gene expression, which in turn is permissive to the expression of the Rh6 gene in the R8 cells. Failing to express spineless above a specific threshold, is permissive to Rh3 expression in R7 cells, which in turn instruct the expression of the Rh5 gene in R8 cells (reviewed in Samoilov et al, 2006). The second example is presented by the work of Raj and coworkers in a recent paper in Nature (Raj et al, 2010), in which they study the effect of modify a genetic network that controls intestinal differentiation in C. elegans. Mutant conditions increase transcriptional noise, which leads to an ON/OFF state of a master regulatory gene. One direct implication is that the incomplete penetrance of some mutations can be explained by stochasticity. Another implication of this work (and underestimated by the authors) is that there are natural buffering systems in organisms that control noise in gene expression, and altering these buffers triggers developmental responses.

Buffering noise is an unexplored field with great implications in development and disease. For example, disruption of buffers in adult humans may lead to cancer development due to stochastic expression of oncogenes. This field is in its infancy, despite the concept of variability relies in the foundations of modern biology, since Darwin studied variations and similarities between species and recognizing that variations are relevant properties of living systems.


Altschuler, S., & Wu, L. (2010). Cellular Heterogeneity: Do Differences Make a Difference? Cell, 141 (4), 559-563 DOI: 10.1016/j.cell.2010.04.033

Huang, S. (2009). Non-genetic heterogeneity of cells in development: more than just noise Development, 136 (23), 3853-3862 DOI: 10.1242/dev.035139

Raj, A., & Vanoudenaarden, A. (2008). Nature, Nurture, or Chance: Stochastic Gene Expression and Its Consequences Cell, 135 (2), 216-226 DOI: 10.1016/j.cell.2008.09.050

Samoilov, M., Price, G., & Arkin, A. (2006). From Fluctuations to Phenotypes: The Physiology of Noise Science’s STKE, 2006 (366) DOI: 10.1126/stke.3662006re17

Novick, A. (1957). Enzyme Induction as an All-or-None Phenomenon Proceedings of the National Academy of Sciences, 43 (7), 553-566 DOI: 10.1073/pnas.43.7.553

Zernicka-Goetz, M., Morris, S., & Bruce, A. (2009). Making a firm decision: multifaceted regulation of cell fate in the early mouse embryo Nature Reviews Genetics, 10 (7), 467-477 DOI: 10.1038/nrg2564

Goentoro, L., & Kirschner, M. (2009). Evidence that Fold-Change, and Not Absolute Level, of β-Catenin Dictates Wnt Signaling Molecular Cell, 36 (5), 872-884 DOI: 10.1016/j.molcel.2009.11.017

Goentoro, L., Shoval, O., Kirschner, M., & Alon, U. (2009). The Incoherent Feedforward Loop Can Provide Fold-Change Detection in Gene Regulation Molecular Cell, 36 (5), 894-899 DOI: 10.1016/j.molcel.2009.11.018

Gujral TS, & MacBeath G (2010). A system-wide investigation of the dynamics of Wnt signaling reveals novel phases of transcriptional regulation. PloS one, 5 (4) PMID: 20383323

Johnston Jr., R., & Desplan, C. (2010). A Penetrating Look at Stochasticity in Development Cell, 140 (5), 610-612 DOI: 10.1016/j.cell.2010.02.018

Raj, A., Rifkin, S., Andersen, E., & van Oudenaarden, A. (2010). Variability in gene expression underlies incomplete penetrance Nature, 463 (7283), 913-918 DOI: 10.1038/nature08781

Global Biodiversity Indicators at-a-glance

ResearchBlogging.orgI really wanted to talk about this article before. A few weeks ago, it was published in Science a work by an extensive work by a high number of researchers, focused in the review and discussion of indicators of global indicators of biodiversity. Citing the article, in 2002 world leaders committed, through the Convention on Biological Diversity, “to achieve by 2010 a significant reduction of the current rate of biodiversity loss”.

Now, 2010 has been named the International Year of Biodiversity. And a team reported in this article, numbers and trends showing the current state of several indicators of biodiversity, grouped into four main categories: indicators of state, pressure, response and benefits.

The indicators of state are related with the state of biodiversity in terms of species and ecosystems. Eight indicators show a decline. For example, the Living Planet Index (mean population trends of vertebrates) show a continuous decline since 1970. The Red List Index, indicating the risk of extinction of mammals, birds, amphibians and corals, also show a decline. Other indicators are Forest Extent, Coral Reef Condition and Water Quality Index.

Indicators of pressure on biodiversity are more related with difficulties upon the improvement of biodiversity. One example is the Exploitation of Fish Stocks, which exhibits a great increase. All the indicators of pressure (Ecological Footprint, Nitrogen Deposition Rate, Alien Species in Europe, and Climate Impact Indicator) show an increase.

Although the numbers are discouraging, some hope arises when we look at the positive numbers. Indicators of response are increasing, and the authors show some data related with improvements in biodiversity. For example, at least 16 bird species extinctions were prevented by conservation actions during 1994-2004. Also, deforestation in Amazonia decreased, protected areas increased and several countries have policies and agreements related with the prevention of spread of alien species.

This post is not intended to be a review of the article. Instead, it offers a view at-a-glance, a general commentary of the article. I advice to all the readers of this post to read the article and to visit the webpage of the Convention on Biological Diversity, where you can download more information about the mission and goals for this year and for the future.

In words of the authors of the article, “our results show that, despite a few encouraging achievements, efforts to address the loss of biodiversity need to be substantially strengthened”.


Butchart, S., Walpole, M., Collen, B., van Strien, A., Scharlemann, J., Almond, R., Baillie, J., Bomhard, B., Brown, C., Bruno, J., Carpenter, K., Carr, G., Chanson, J., Chenery, A., Csirke, J., Davidson, N., Dentener, F., Foster, M., Galli, A., Galloway, J., Genovesi, P., Gregory, R., Hockings, M., Kapos, V., Lamarque, J., Leverington, F., Loh, J., McGeoch, M., McRae, L., Minasyan, A., Morcillo, M., Oldfield, T., Pauly, D., Quader, S., Revenga, C., Sauer, J., Skolnik, B., Spear, D., Stanwell-Smith, D., Stuart, S., Symes, A., Tierney, M., Tyrrell, T., Vie, J., & Watson, R. (2010). Global Biodiversity: Indicators of Recent Declines Science, 328 (5982), 1164-1168 DOI: 10.1126/science.1187512

Secretariat of the Convention on Biological Diversity (2010) Global Biodiversity Outlook 3., & Montréal, 94 pages. (2010). Global Biodiversity Outlook 3 Convention on Biological Diversity

References Management in Mac: new guide on using Zotero

As I mentioned before, the most successful posts on this blog (in terms of visits and comments) are those related with reference management in Mac. A long time ago, I published a post in which I wrote about the advantages of Papers, or more exactly, the disadvantages of Mendeley in Mac, and I recommended using Papers+Zotero in Mac. But I had a problem with the new versions of Zotero.

Now, I solved the problem with Zotero, and I will explain the steps to have a fully functional Zotero+Papers combination for making bibliographies in Mac.

NOTE: The following steps are valid to use the latest version of Zotero with Word 2004. Since the Office for Mac is very bad, I have no intentions to purchase the Word 2008. But plugins and instructions are available for using Zotero with Word 2008 in the official site.

Step 1. Updating.

In order to have a fully functional set up, you have to install the newest version of Firefox (3.6.6.). You also have to install the most recent version of Zotero, and the Phyton extension and the latest word plugin. The last two (PhytonExt+Word Plugin) are available in this page of Zotero, under the “Mac OSX” section. Follow all the instructions; it’s easy.

Step 2: Updating the library in Zotero.

I recommend deleting all your libraries and start from scratch. If you have Papers, take a time in updating and matching all your PDFs. Once you are ready, go to File>Export>BibTeX Library* (it’s the one that works best for me). *Caution, I have both Papers and Zotero in Spanish, so some names and menus could be different.

Once in Zotero, in the Actions menu, I go to Import. Select the *.bib library that you exported from Papers, and then wait. Depending on the size of the library, it will take a little time to have an updated library. But, when it’s finished, you will be ready to work.

Step 3. Working in Word.

You are now ready to use Zotero in Word. In Tools>Customize, select the Zotero Bar, and place it where you feel it’s more comfortable.

When you need to insert a citation, just click in the “Zotero Insert Citation” icon (the first one, from left to right) in the Zotero Bar. A window will show up. In this window, you can select the citation style. When you are ready, a new window will open, showing your library, and you can now select the reference you want to cite.  When you are finished, and need to insert the final bibliography, just click in the “Zotero Insert Bibliography” icon (the third icon), and then you are ready. You have a muanuscrpit with references and a bibliography.

Please note that in the official site in Zotero, there are full instructions in the usage of Zotero and the plugin. Instructions here.

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