human biology - How does Humira work when injected into patients with rheumatoid arthritis?

Afaik. RA and psoriasis are probably caused by a malfunction of genes which regulate IL-23 production. IL-23 is required for Th17 cells to survive. Th17 cells produce a lot of things which result in inflammation and since TNF-α is a key mediator in inflammation and break down of joints, reducing the amount of available TNF-α reduces the inflammation.

(Th17 cells produce IL-17, IL-21, IL-22, IL-6 and TNF-α. Th17 cells are playing against Treg cells, which try to protect self cells. IL-17 promote osteoclastogenesis, and osteoclasts break down bone. According to serveral wikipedia articles IL-17 induces the production of other cytokines such as IL-6, IL-1β, TNF-α. IL-21 is required for sustained CD8+ T cell effector activity. IL-22 is a mediator of cellular inflammatory responses. IL-6 modulates the resistance of T cells against apoptosis, induces activation of T helper cells and promotes osteoclastogenesis. TNF-α is an endogenous pyrogen which is able to induce fever, apoptotic cell death, cachexia, inflammation and inhibits tumorigenesis and viral replication. IL-1β is a mediator of the inflammatory response, and it is involved in the regulation of apoptosis as well.)

Adalimumab is an immunoglobulin, which binds to TNF-α, and so it prevents it to bind TNF-α receptors and cause inflammation. After it is bound to its target you cannot reuse it, that's why you need daily doses of it. It is degraded by liver and kidney cells, or probably by phagocytes as well.

There are other TNF-α blocking pharmaceuticals as well. There are IL-23 inhibitors, one of them is called ustekinumab. It is an immunoglobulin too and it is used by treating psoriasis. By RA it is currently under clinical trial, but I guess it will work by RA as well. There is an IL-23 inhibitor which is not an immunoglobulin and can be taken orally, it is called apilimod. Sadly it failed the clinical trials, it had only mild effect. It probably does not reach the inflammation in sufficient amount. Maybe later there will be an effective delivery method and so a drug which can be taken orally.

There are alternative natural therapies: TNF-α inhibitors which you can take orally, for example γ-linolenic acid, ω−3 fatty acids, chondroitin sulfate, etc... These can be useful by mild cases of RA. Probably fever therapy works by mild cases as well. Afaik. cryotherapy has nice results in treating RA and its positive effect lasts much longer than the effects of any drugs, so if you aren't afraid of cold, that is a nice alternative therapy as well.

Blood Pressure: Significance of difference between systolic and diastolic

The difference between systolic (the upper number) and diastolic (the lower number) pressures is known as the pulse pressure:

Systemic pulse pressure = P_systolic - P_diastolic

For a typical blood pressure reading of 120/80 mmHg the pulse pressure is therefore 40 mmHg.

It is proportional to stroke volume, the amount of blood pumped from the heart in one beat, and inversely proportional to the compliance or flexibility of the blood vessels, mainly the aorta.

A low (also called narrow) pulse pressure means that not much blood is being expelled from the heart, and can be caused by a number of factors, including severe blood loss due to trauma, congestive heart failure, shock, a narrowing of the valve leading from the heart to the aorta (stenosis), and fluid accumulating around the heart (tamponade).

High (or wide) pulse pressures occur during exercise, as stroke volume increases and the overall resistance to blood flow decreases. It can also occur for many reasons, such as hardening of the arteries (which can have numerous causes), various deficiencies in the aorta (mainly) or other arteries, including leaks, fistulas, and a usually-congenital condition known as AVM, pain/anxiety, fever, anemia, pregnancy, and more. Certain medications for high blood pressure can widen pulse pressure, while others narrow it. A chronic increase in pulse pressure is a risk factor for heart disease, and can lead to the type of arrhythmia called atrial fibrillation or A-Fib.

botany - Why is the floral biodiversity of grazed grassland higher than that of mown grassland?

I have collected some data to compare the biodiversity of a field in which the plagioclimax is maintained by machine mowing with a field in which the plagioclimax is maintained by sheep grazing.

What I found was that there was a significant increase in floral biodiversity in the field which was managed by agricultural grazing when compared to the floral biodiversity of the machine-mown field.

I am trying to explain my findings, and I believe that it is due to the comparitively short amount of time that machine-mowing has been a grassland management technique, so there has been little time for natural selection to take place and for species to develop adaptations to machine-mowing (such as being low-lying, or extremely fast-growing). Whereas the field which is managed through sheep-grazing, contains multiple competing species which have adapted over time to grazing sheep, such as Cirsium arvense.

Moreover, the field which is managed by grazing has nutrients returned to it through defecation of the grazing animals, allowing for more favourable conditions for growth.

Is my explanation valid? Are there any other reasons why the floral biodiversity of a field managed by sheep grazing would be higher than one managed by machine-mowing?

Thanks in advance!

evolution - Why was polyploidy not lethal in certain octodontid rodents?

Actually, that is not what is discussed in the question you linked to. The following is a quote from the very comprehensive accepted answer (emphasis mine):

Polyploidy arises easily in both animals and plants, but reproductive
strategies might prevent it from propagating in certain circumstances,
rather than any reduction in fitness resulting from the genome
duplication.

In fact, try rereading that answer and the references therein, it answers your general question.

There is a popular theory (mostly accepted) that there have been whole genome duplication events (WGDs) in the vertebrate ancestry. If true, it means that all mammals are the descendents of polyploid ancestors. For a very nice review of WGDs in vertebrate evolution, see here [1]. Octomys is simply the only known mammal with a more recent WGD event. As for what makes it special (taken from [2]):

Our data demonstrate that parental-specific silencing of at least one
gene and normal X chromosomal dosage mechanism are conserved in the
tetraploid genome. We hypothesize a concerted action of genetic and
epigenetic mechanisms during the process of functional diploidization
of this tetraploid genome.

1) Van de Peer Y, Maere S, Meyer A., The evolutionary significance of ancient genome duplications., Nat Rev Genet. 2009 Oct;10(10):725-32.

2) Bacquet C, et al., Epigenetic processes in a tetraploid mammal, Mamm Genome. 2008 Jun;19(6):439-47.

human biology - How does sodium in one's diet affect blood pressure?

Salt will cause high blood pressure, but only under certain circumstance.

physiologic hormonal compensations for increased blood volume:

• Atrial natriuretic peptide -- increases sodium excretion, hence this is INCREASED with high blood volume


• Antidiuretic horomone -- ADH increases water reabsorption in the kidney, hence this will be DECREASED with high blood volume


• Renin/Aldosterone -- increases sodium reabsorption from ultrafiltrate back into blood, hence it will be DECREASED

these explainations are a bit reverse (saying that these horomones have these effects and that is why they are released) for the sake of simplicity, and I'm not discussing the mechanism of release of these horomones (aka under what circumstances they are released in the place where they are released from)...

while these horomones help with the kidney regulation of sodium balance and blood volume, this still depends on the kidneys being given the circumstance where they can be effective.

Pathologic circumstances, when elimination of excess sodium fails:

Some people simply have a higher sodium sensitivity and there are a variety of factors that have been statistically correlated to sodium sensitivity, but often the mechanism is unknown. Here are various factors statistically correlated to affect salt sensitivity:
http://physrev.physiology.org/content/85/2/679

the above article shows that no organ systems need be compromised for excess sodium to raise blood pressure, but just for the sake of discussing more macroscopic things I want to discuss these organ systems based reasons for the kidney being unable to compensate for excess sodium in the diet=

• The kidney:
  A patient with renal disease may not be able to regulate the excretion of sodium. Even in normal humans, the kidney's capacity to excrete sodium declines with age, and smaller increases in salt intake induce a rise in arterial pressure, as GFR (the renal filtration of the blood sent to the kidney) falls by about 40%, though individual variations are wide and some people lose less.

Other than the kidney:
Other diseases can also interfere with renal excretion of sodium. A problem with maintaining blood volume will cause constriction of the renal artery. This would occur before a drop in blood pressure would occur, as this is a way of preventing a drop in blood pressure. This occurs in congestive heart failure and liver cirrhosis.

• A patient with congestive heart failure may not have adequate renal
  perfusion. Hence, to maintain adequate blood pressure the renal artery is constricted.


• Also, liver cirrhosis may decrease renal perfusion
  because of the lack of blood proteins (proteins found inside the
  blood vessels that keep water in the blood vessels via osmosis)
  holding fluids in the intravascular space and having them escape into
  the extra-vascular (outside the blood vessels but still outside the
  cells of the body) space. Again, to maintain adequate blood pressure the renal artery is constricted.


• burns, also because of loss of blood proteins--> leakage of intravascular fluid to extravascular space--> decreased blood volume and increased sympathetic nervous system output--> reduction of renal blood flow... same as for cirrhosis

In addition to reduction of salt in the diet, diuretics (ex. loop and thiazide) can help the body excrete even more sodium into the urine than what your body can do on it's own.

this article describes the renal handling of excess salt in the diet:
http://booksite.elsevier.com/brochures/thekidney/PDFs/TheKidneyCh36_P088488.pdf

entomology - How do ants sense imminent rainfall?

This article claims that ants do sense approaching rain and modify their activities in preparation. The claim is not sourced. This weather site also speaks of ant mound-building before a rain but frankly places it in the "some folks say" category. The AntBlog is associated with AntWeb, a large multi-university-affiliated database. The author of the linked blog states that ants can sense humidity with their antennae, which strikes me as a plausible means of anticipating rain.

That ants might sense changes in barometric pressure is an intriguing idea but has not to my knowledge been demonstrated.

A 2010 article in Journal of Neurophysiology reports an almost unbelievable sensitivity to temperature in ant antennae, allowing them in principle to sense minute temperature changes ($0.005^o$C) over a wide range of temperatures and over 0.2 second time intervals (5Hz). This is said to assist them in orientation in their microenvironment but I think it goes a long way to accounting for an ability to detect looming weather fronts. Humans can sometimes 'smell' rain and we can detect gross temperature changes that almost always accompany rain, but to be able to detect humidity and micro-scale temperature changes would give the ants a real advantage in forecasting. After all, not all rainstorms are preceded by a dramatic drop in temperature but probably the majority are preceded by minute step-wise drops in temperature that evidently the ants can sense.

So while I think the building activity may be anecdotal (and probably true for some species) the ability to sense humidity changes and micro-scale temperature changes accounts for their ability to sense rain ahead of time.

Ants are very well-studied and it's hard to rule out that one has missed something. There are a few "ask the expert" questions on this topic online and no one seemed sure.

zoology - Polymorphism in cnidarians?

It seems like your question might contain two separate and linked issues, both of which are perhaps equally confusing and equally interesting. They're both really discussion questions in a sense, but they've also both been dealt with in the literature in thoughtful ways, so here's a stab at an "answer".

Issue One: how does your species concept deal with polymorphism?

This may depend on which species concept you're using. And, to some extent, the choice of which species concept you use depends on what kind of organism you're dealing with (for instance, organisms that reproduce asexually have a whole different set of issues and challenge several species concepts).

Various papers by Kevin de Queiroz deal very well with species concepts. In 'The General Lineage Concept of Species' (which is also summarized on this page), he argues that although there are many different species concepts that can be better applied to different situations, they all share the basic tenet of defining a "segment of a population-level lineage". In other words, each concept is attempting to put a continuum into slightly different categorical bins, but they all recognize the existence of the same continuum (the lineage). (Also see his 'Species Concepts and Species Delimitation'.)

I think most species concepts have no trouble dealing with polymorphism because the different morphs are all part of the same lineage, that is, "a series of entities forming a single line of direct ancestry and descent" (de Queiroz 1999).

---

Issue Two: how does your concept of the individual organism deal with colonialism?

In 'Does Biology Need an Organism Concept?' Pepper and Herron make a similar point to that of de Queiroz. They argue that multiple definitions (concepts) exist, and that these concepts all attempt to categorically bin what is in fact a continuum. Like de Quieroz, they argue that most definitions recognize the same underlying continuum, and that the difference is in the categorical bins.

In the case of the organism concept, this continuum is based on two criteria: increasing genetic homogeneity, and increasing physiological integration.

So, for instance you could have two organism concepts (in the picture below, lighter yellow and darker yellow) that agree that Physalia falls in the same location along these axes, but disagree on exactly where to draw the boundary between their "multiple organisms / colony" zone (yellow), and their "individual organism" zone (white).

I'll finally get to my point, paraphrasing both de Queiroz and Pepper and Herron. For both concepts of the species and of the organism, arguing about whether one concept is better than another is endless (especially on a site that aims at answers rather than discussion). However, recognizing that there are different concepts, understanding that what these concepts do is to bin the same continuum in different ways, and being clear about which concept you decide to use is very useful.