Tuesday, September 16, 2008

Comments on the Photo-protective qualities of epidermal Melanin Content of skin

Based on extracts from Yamaguchi et al. 2006, we have the following:

— DNA damage in the upper epidermis immediately after UV exposure was similar among racial/ethnic groups but levels of DNA damage in the lower concentration of the epidermis was inversely proportional to the melanin content.

Courtesy of Yamaguchi et al. 2006: Figure 1. A) Representative images of CPD DNA damage in fair, intermediate and dark skin immediately and 7 d after UV exposure; green and red fluorescence represent CPD and DNA, respectively. (———) demarks the top of the granular layer of the epidermis, (- - - -) demarks the epidermal:dermal junction, and (· · · · ·) represents the division between the upper and lower epidermal layers. B) Representative images of CPD (green) in melanocytes (stained red for tyrosinase) immediately after UV in fair, intermediate and dark skin.

— Pulse lasers cause highly selective injury to cells containing melanosomes suggesting that the UV energy absorbed by melanin in the upper epidermis causes photothermolysis (heat damage) to pigmented cells.

— The oncogene p53 plays important roles in responses to UV-induced DNA damage and induction of DNA repair. There is an overall nuclear accumulation of p53 in response to UV. More than 13 sites of p53 are known to be phosphorylated, one of them being a critical site at Ser-46, which is associated with the induction of apoptosis.

More p53 accumulated in the nuclei of cells in fair skin than in dark skin at 1 d and at 7 d after UV exposure. However, phosphorylation of p53 at Ser-46 was not seen in fair skin, whereas it was readily seen in dark skin 1 d after UV exposure…

Phosphorylation of p53 at Ser-46, which is associated with the induction of apoptosis, occurred at low levels in fair skin after low doses of UV exposure but was significant in dark skin, suggesting that p53 phosphorylation site is involved in UV-induced apoptosis in epidermis with abundant levels of melanin.

TUNEL assays showed that significantly more apoptotic cells were found in Black skin equivalents than in Asian or White skin equivalents at both UV doses...

nuclear accumulation of p53 is less in dark skin than in fair skin, suggesting that the overall activation of p53 following UV-induced DNA damage is greater in fair skin. The sustained activation of p53 may also in part cause the higher incidence of photo carcinogenesis in fair skin.

melanin content is responsible for the apoptosis. Cells containing melanin in the upper epidermis of dark skin tended to undergo more apoptosis after UV than do those of fair skin. Thus, the presence of melanin facilitates the apoptotic effect of UV on cells but whether that results from photothermolysis or whether other properties of melanins are involved will require further study.

DNA damage in the upper epidermis immediately after UV exposure was similar among racial/ethnic groups but levels of DNA damage in the lower concentration of the epidermis was inversely proportional to the melanin content.
Taken together,…

— UV-induced DNA damage in the lower epidermis (which contains keratinocyte stem cells and melanocytes) is not effectively prevented in fair skin because of the low melanin content in the upper (and lower) epidermis.

DNA damage in the upper epidermis is quite similar among all types of skin, which indicates that epidermal pigmentation is an efficient UV filter for underlying cells.

— UV-induced apoptosis was virtually absent in fair skin after low UV doses, but was significant in dark skin, facilitating the effective removal of UV-damaged cells in dark skin.

— Virtually all epidermal cells had significant DNA damage in fair skin but only ~1% of them became apoptotic whereas less than 50% of epidermal cells in dark skin had significant DNA damage, yet ~ 5% of those cells were apoptotic.

— The combination of relatively low DNA damage and efficient removal of UV-damaged cells contributes to the decreased incidence of skin cancer in darker skin.

we conclude that the upper epidermis of dark skin is significantly more photoprotective for the deeper tissue against UV damage than that of fair skin.

And now, on the understanding gleaned from the above, some personal observations about the photo-protective qualities of epidermal melanin content:

Essentially, the side effect of UV-radiation damage of DNA in epidermal cells is the activation of the p53 gene to presumably suppress cell division of damaged DNA, and allow for repair, which would explain the accumulation of this type in cell nuclei after UV exposure. However, given the greater DNA damage in fair skin due to reduced melanin content, more p53 are activated than the case is for dark skin; the other problem here though, seems to be that there is also a strong correlation between the phosphorylation of p53 at the Ser-46 locus of the gene, which appears to be critical for apoptosis, and epidermal melanin content; the greater the epidermal melanin, the greater chances of greater occurrence of nuclear p53 genes phosphorylated at their Ser-46 locus. The precise triggering aspect of melanin on apoptosis is something that is subject to further investigation, according to Yamaguchi et al.: the presence of melanin facilitates the apoptotic effect of UV on cells but whether that results from photothermolysis or whether other properties of melanins are involved will require further study.

Since this development [phosphorylation] at the Ser-46 locus appears to be much rarer on p53 genes in epidermal cells of fair skin, the prospect of apoptosis occurring after UV exposure is substantially lower, if not rare. This means that damaged DNA are allowed to spread via cell division and so, defects being passed onto daughter cells; on the other hand, greater presence of phosphorylation of the p53 gene at its Ser-46 locus in dark skin epidermal cells allows for effective removal of UV-induced damaged DNA. So, it would appear that the hindrance of p53 gene in fair skin epidermal cells to play a role in removal of cells containing damaged DNA in the process of assisting in DNA repair, at least in part, interrupts the optimal balance between cell division and apoptosis, thereby contributing to photo-carcinogenesis. [see: Yamaguchi et al. 2006; Human skin responses to UV radiation: Pigment in the upper epidermis protects against DNA damage in the lower epidermis and facilitates apoptosis]
*Related reading:

Skin pigmentation gene alleles

Skin pigmentation gene alleles — Part 2

The possibility that Ancient Egyptian was a regional Lingua Franca...

Often times, people discuss how lower Nile Valley polities united with the Upper Nile Valley ones, with the initiative coming largely from upper Nile Valley ruling elites; yet, it almost never comes up or crosses the mind, that these discrete polities might have well very likely spoke distinctive dialects, if not language types altogether, as well. This would mean that there would have been a common language to facilitate trade during the pre-dynastic era, and a common language to effectively unify all the previously discrete autonomous Nile Valley polities under one national language. This language would have no doubt, functioned as a regional lingua franca; the same could be said of the regions south of Egypt, which contemporary Egyptologists have a habit of generically referring to as "Nubia".

The questions that ought to come to mind, should be for example, as follows:

  • Did pre-dynastic Lower Egyptians "originally" speak the same languages as their pre-dynastic Upper Egyptian counterparts?
  • Did the pre-dynastic Lower Egyptian polities amongst themselves speak a single language, or was there only a single pre-dynastic Lower Egyptian polity [which would seem very unlikely, given the different archaeological complexes of the so-designated regions] with a single language? As for predynastic Upper Egypt, it is well known that not a single polity existed therein at the time; so, did these polities speak the same language, or did they adopt a sub-regional lingua franca in Upper Egypt, all the way to parts of northern Sudan?
  • Did Egypt, upon unification, take the language of the dominant ruling elites as the regional lingua franca, which would become Egyptic, or was this simply developed by the merging of language elements from all the regions brought under unity? The same scenario can be played in Kush, where Kushitic/Meroetic language would serve as the regional lingua franca. This was a polity, as can be seen from artistic impressions, to be quite diverse. Could something like what happened in Ethiopia, and elsewhere in Africa, i.e. West Africa and South Africa, have happened in these regions, with Amarinya becoming a sort of lingua franca for the various groups with their distinctive tongues?

Consider for example, the following recap on at least one observation made about predynastic developments in lower and upper Egyptian regions:

With some emphasis placed on language…

Relevant reading from Keita and Boyce, Genetics, Egypt, And History: Interpreting Geographical Patterns Of Y Chromosome Variation, 2005:

“Later there is some movement into Africa after the domestication of plants and Ovacaprines, which happened in the Near East nearly 2000 years before it occurred in Egypt (Hassan 1988, Wetterstrom 1993). Early Neolithic levels in northern Egypt contain the Levantine domesticates, and show some influence in material culture as well (Kobusiewicz 1992). Ovacaprines appear in the western desert before the Nile valley proper (Wendorf and Schild 2001). However, it is significant that ancient Egyptian words for the major Near Eastern domesticates - Sheep, goat, barley, and wheat - are not loans from either Semitic, Sumerian, or Indo-European. This argues against a mass settler colonization (at replacement levels) of the Nile valley from the Near East at this time. This is in contrast with some words for domesticates in some early Semitic languages, which are likely Sumerian loan words (Diakonoff 1981).

This evidence indicates that northern Nile valley peoples apparently incorporated the Near Eastern domesticates into a Nilotic foraging subsistence tradition **on their own terms** (Wetterstrom 1993). There was apparently no “Neolithic revolution” brought by settler colonization, but a gradual process of neolithicization (Midant-Reynes 2000).

(Also some of those emigrating may have been carrying Haplotype V, descendents of earlier migrants from the Nile valley, given the postulated “Mesolithic” time of the M35 lineage emigration). It is more probable that the current VII and VIII frequencies, greatest in northern Egypt, reflect in the main (but not solely) movements during the Islamic period (Nebel et al. 2002), when some deliberate settlement of Arab tribes was done in Africa, and the effects of polygamy. There must also have been some impact of Near Easterners who settled in the delta at various times in ancient Egypt (Gardiner 1961). More recent movements, in the last two centuries, must not be forgotten in this assessment.

And Continued! Keita and Boyce, on the peopling of the Nile Valley…

“Archeological data, or the absence of it, have been interpreted as suggesting a population hiatus in the settlement of the Nile Valley between Epipaleolithic and the Neolithic/predynastic, but this apparent lack could be due to material now being covered over by the Nile (see Connor and Marks 1986, Midant-Reynes 2000, for a discussion). Analogous to events in the Atacama Desert in Chile (Nunez et al. 2002), a moister more inhabitable eastern Sahara gained more human population in the late Pleistocene-early Holocene (Wendorf and Schild 1980, Hassan 1988, Wndorf and Schild 2001). If the hiatus was real then perhaps many Nile populations became Saharan.

Later, stimulated by mid-Holocene droughts, migration from the Sahara contributed population to the Nile Valley (Hassan 1988, Kobusiewicz 1992, Wendorf and Schild 1980, 2001); the predynastic of upper Egypt and later Neolithic in lower Egypt show clear Saharan affinities. A striking increase e of pastoralists’ hearths are found in the Nile valley dating to between 5000-4000 BCE (Hassan 1988). Saharan Nilo-Saharan speakers may have been initial domesticators of African cattle found in the Sahara (see Ehret 2000, Wendorf et. Al. 1987). Hence there was a Saharan “Neolithic” with evidence for domesticated cattle before they appear in the Nile valley (Wendorf et al. 2001). If modern data can be used, there is no reason to think that the peoples drawn into the Sahara in the earlier periods were likely to have been biologically or linguistically uniform.

…A dynamic diachronic interaction consisting of the fusion, fissioning, and perhaps “extinction” of populations, with a decrease in overall numbers as the environment eroded, can easily be envisioned in the heterogenous landscape of the eastern Saharan expanse, with its oases and Wadis, that formed a reticulated pattern of habitats. This fragile and changing region with the Nile Valley in the early to mid-Holocene can be further envisioned as holding a population whose subdivisions maintained some distinctiveness, but did exchange genes. Groups would have been distributed in settlements based on resources, but likely had contacts based on artifact variation (Wendorf and Schild 2001). Similar pottery can be found over extensive areas. Transhumance between the Nile valley and the Sahara would have provided east-west contact, even before the later migration largely emptied parts of the eastern Sahara.

Early speakers of Nilo-Saharan and Afroasiatic apparently interacted based on the evidence of loan words (Ehret, personal communication). Nilo-Saharan’s current range is roughly congruent with the so-called Saharo-Sudanese or Aqualithic culture associated with the less arid period (Wendorf and Schild 1980), and therefore cannot be seen as intrusive. Its speakers are found from the Nile to the Niger rivers in the Sahara and Sahel, and south into Kenya. The eastern Sahara was likely a micro--evolutionary processor and pump of populations, who may have developed various specific sociocultural (and linguistic) identities, but were genealogically “mixed” in terms of origins.

These identities may have further crystallized on the Nile, or fused with those of resident populations that were already differentiated. The genetic profile of the Nile Valley via the fusion of the Saharans and the indigenous peoples were likely established in the main long before the Middle Kingdom…

…Hoffman (1982) noted cattle burials in Hierakonpolis, the most important of predynastic upper Egyptian cities in the later predynastic. This custom might reflect Nubian cultural impact, a common cultural background, or the presence of Nubians...

Apparently, all these different groups would have found a way to communicate with each other.

Considering that there was an inter-trade network along the Nile Valley long before unification, another possibility is the idea of a 'trade language' being developed, and then developing into what would become Egyptic of Pharaonic Egypt.

Clyde Winters chimes in with this interesting note:

You are on to something.

It will be difficult to really elaborate this theme given our knowledge about Egyptian language. But the use of two different "cursive" scripts: Hieratic and Demotic, by two different ruling groups, may indicate that different languages and traditions of writing may have existed in Egypt in ancient times.