Can you link the original source of this diagram? +/- is usually used to denote positive/negative interactions, respectively. Some people also use arrowhead for positive interaction and a "tee" (⊣) end for a negative interaction. So there is no universal standard. In your case it looks weird. For instance, P450 system should reduce toxicity but in the diagram the interaction is depicted with a +.

Hi WYSIWYG. The first diagram was taken from an example supplied from the Open University. I supplied the relevant information that accompanied the diagram. The second diagram, I drew myself to answer the question. I placed as much information as possible so my question might make more sense now. I hope this is what you need to provide insight. Many thanks for your help!

The original diagram is inconsistent with the use of symbols. As I mentioned, P450 should have a negative effect on toxicity but it is indicated by a +. The interaction between deformed wing virus and mortality (which is a positively correlated interaction) is also denoted by a +. Now, again, immune response also has a + interaction on the virus. Overall, this diagram is inconsistent with the usage of the symbols and is hence wrong.

I'm voting to close this question as off-topic because it is based on a non-standard and incorrect premise that is not even a part of a published text.

Hi WYSIWYG. In this systems diagram (diagram 1: which is definitely a published text with the OU and designed by a doctor in his field), the description says "+" and "-" signs are read as "positive" and "negative" in terms of the recipient box in the diagram. There are some boxes with a negative statement/factor, e.g., "Deforming wing virus", it has "+" on the arrow from "Immune response". That means that immune response allows deforming wing virus to develop. So "+" here confirms the strength of the negative statement in the box.

This question may help many people like me who are suffering from confusion over the theory of "+" and "-" symbols in systems diagrams. I really do appreciate your help and advice. Many thanks

I understand. But the most common usage is that + denotes a positive effect (causal) on the on the node where the edge is directed to (conversely for -). However, I cannot be sure about this diagram because it doesn't really rationalize these interactions. For example, I would expect immune response to suppress the virus and P450 system to reduce toxicity. Both these interactions should have a - but they have a +. The premise is, hence, unclear. By published text, I mean something published in a book or a peer-reviewed article (at least a place that has figure legends).

So, I also asked a fellow colleague and he explained it like this: a systems diagram is not constrained to involving a biotic interaction. For example, the well know positive feedback loop involving sea ice and warming, whereby warming leads to reduction in sea ice, which increases surface albedo (water is darker than ice), further warming the surface and more melting. This could be represented as [warming] -- (-) -- [sea ice] -- (-) -- [albedo] -- (+) -- [warming].

Are you thinking along the same lines?

I used to work on systems biology.

In which graphs like that are very common.

However you have to be clear what each node represents.

Usually a node represents an entity of the system and an edge represents an interaction.

In biochemical networks nodes are biomolecules.

As you know chemical reactions cause a molecule to convert to another.

These are typically represented by an arrow.

In biochemical network diagrams node to node arrows (edges) represent conversion.

Conversion does not have a negative or positive aspect.

I am using the information I have been given, that is "+" = positive effects and "-" = negative effects. I am still confused! The way I am reading diagram 1 is fungicide reduces "-" the inhibition of the P450 Detox System, which increases toxicity "+" and therefore, increases "+" mortality

There are other arrows that are directed from a node to an edge. These represent the regulatory effect. For e.g. an enzyme increasing the rate of a certain reaction.

If we forget that level of complexity and just think about purely regulatory networks i.e. there are no conversions; just regulatory interactions.

Then a positive interactions from one node to the other means that the former promotes the production/occurrence of the latter.

Okay, so we are clear up till here?

Just like when you produce are diagram for the pathways of immunity

Yes! It is making more sense

Thank you for your help

@AliceHobbs I don't know what pathways are you talking in particular. There can be different kinds of representations for different processes.

However, the primary job of P450 system is to detoxify. So the interaction from p450 to toxicity should be "-".

I studied immunity briefly as a third-year biological sciences student and I decided to not finish the course because there were so many pathways that an immune response can take and I specialised in ecology and wildlife conservation. It was such a big step from nothing to higher level immunity when most of my class were training to be doctors.

In these diagrams each interaction is independent of others.

This is why I got confused in the first place because I thought it would be negative "-" too

However, in my textbook the symbol is "+"

@AliceHobbs check the figure legends of the textbook. If it doesn't rationalize the diagram then basically it is a shitty diagram.

And diagrams are supposed to help understanding the process not complicate it.

So you see here that the effects and symbols are inconsistent.

Likewise, immune response should suppress the virus not help it.

I will! I also don't understand why MNI/Fiprinol would have a negative effect on social immunity, and then produces a positive "+" effect on Nosema. I guess that might be because social immunity is reduced and increases the spread of Nosema "+" in the bee colony! Are these inconsistent too?

Yes! I do get your point. Perhaps under the right circumstances, the immune response does suppress the virus, but I have been looking at the "+" and "-" symbols in diagram 1. Perhaps the if the concentration of fungicide is too high, the p450 can no longer inhibit or detoxify the fungicide and toxicity increases "+". This is the only explanation I can think of. Is this possible? Are there instances when p450 can no longer inhibit toxins?

@AliceHobbs Yes there are instances in which the P450 system can make the xenobiotic more toxic (ncbi.nlm.nih.gov/pmc/articles/PMC5402866). However, if the diagram talks about such specific cases it should have mentioned the exact enzyme and the xenobiotic.

Azole fungicides are actually inhibitors of some cytochrome p450 enzymes (and hence kill the fungi).

These fungicides also seem to have the same inhibitory activity in insects too.

And possibly humans too.

Not all fungicides inhibit p450 so firstly, such a generalization is incorrect.

Now, normally p450 system is involved in detoxification (unless the specific cases of the opposite are mentioned).

Azole by inhibiting p450 is further increasing the toxicity (of itself or other drugs).

I do get your point! I have sat in confusion over this issue.

I just found this abstract

If you were to draw a direct edge from fungicide to toxicity you would have a +

However, there cannot be a "+" edge between p450 and toxicity.

@AliceHobbs good.. So this means that p450 detoxifies. However, if there was an enzyme that in fact potentiates the neo-nicotinoid insecticide, then it would further increase toxicity. As you now know that there are many p450 enzymes. It is possible (although I am not aware of it) that two enzymes lead to opposite consequences. Then the net effect may be a balance of the two enzymes. However, there is no such complexity here.

It's a really interesting study! I read another recent study that the immune response in bees to neonicotinoid insecticide was different country to country indicating differences in bee health per country