Dermatoglyphs of the population from the island of Rab (Croatia)

As a part of multidisciplinary anthropological research of population structure on Croatian island of Rab, finger and palm prints from 548 inhabitants (225 males and 323 females) of six villages on Rab were collected and their qualitative dermatoglyphic traits analysed. We calculated frequencies of patterns (whorls, loops and arches) on fingers, frequencies of patterns in the interdigital areas, Thenar and Hypothenar of the palms and frequencies of position of the axial triradius “t” (t, t′, t″ and other t) for male and female population of each village. Statistical analysis was performed by using Chi-square test, and Hiernaux Δg biological distances between pairs of populations were determined. The results of this study show existence of statistically significant diversity among the village populations in qualitative dermatoglyphic traits both for males and females. This variability found in the population from the island of Rab can be explained by influence of the microevolutionary factors through endogamy and the way of migrational flow on the island in course of history. Subpopulation of Barbat in the eastern part of Rab, which is the closest to the mainland, is probably different because of a high migration rate from the mainland during the past centuries. Subpopulations of Lopar, Supetarska Draga and Kampor were the most isolated subpopulations, situated in three different valleys in the west of Rab, and therefore genetic drift could have been more influential there and responsible for noticed differences.     

Ethnohistorical processes,demographic structure and linguistic determinants of the Island of Vis

The present paper aims at describing the most relevant background data on geomorphological, economic, ethnohistoric, demographic and linguistic features of the island of Vis. As an introduction to future holistic anthropological research on the island, it seeks to identify both internal and external impulses of change and/or continuity of the island population structure within a wider socio-cultural and historical context. The ethnohistorical and demographic data indicate a higher degree of isolation throughout history as compared to other islands in the region and a continuous depopulation trend during the last century. The analysis of the existing linguistic data on two main settlements shows a certain amount of intradialectal micro-differentiation, which is mainly due to various social and non-linguistic reasons.     

Genetic diversity and differentiation of 12 eastern Adriatic and western Dinaric native sheep breeds using microsatellites

Nuclear genetic diversity and differentiation of 341 sheep belonging to 12 sheep breeds from Croatia and Bosnia and Herzegovina were examined. The aim of the study was to provide the understanding of the genetic structure and variability of the analysed pramenka sheep populations, and to give indications for conservation strategies based on the population diversity and structure information. The genetic variation of the sheep populations, examined at the nuclear level using 27 microsatellite loci, revealed considerable levels of genetic diversity, similar to the diversity found in other European indigenous low-production sheep breeds. Population-specific alleles were detected at most loci and in breeds analysed. The observed heterozygosity ranged from 0.643 (in Lika pramenka) to 0.743 (in Vlasic pramenka), and the expected heterozygosity ranged from 0.646 (in Lika pramenka) to 0.756 (in Dalmatian pramenka). Significant inbreeding coefficients were found for half of the populations studied and ranged from 0.040 (Pag island sheep) to 0.091 (Kupres pramenka). Moderate genetic differentiation was found between the studied sheep populations. The total genetic variability observed between different populations was 5.29%, whereas 94.71% of the variation was found within populations. Cres island sheep, Lika pramenka and Istrian sheep were identified as the most distinct populations, which was confirmed by the factorial analysis of correspondence and supported through a bootstrapping adjustment to correct for the difference in the sample sizes. The population structure analysis distinguished 12 clusters for the 12 sheep breeds analysed. However, the cluster differentiation was low for Dalmatian, Vlasic, Stolac and Krk pramenka. This systematic study identified Lika pramenka and Rab island sheep as those with the lowest diversity, whereas Istrian sheep and Pag island sheep had the highest. Conservation actions are proposed for Istrian, Rab and Cres island sheep, Lika and Kupres pramenka because of high estimated coefficients of inbreeding.     

Morphometric dimensions of metacarpal bones in the population structure analysis (island of Krk, Croatia)

The population structure analysis by means of the osteometric dimensions of metacarpal bones in the population groups of the northern Adriatic island of Krk, Croatia was performed. The sample consisted of randomly sampled adult islanders (94 males and 79 females) aged from 18 to 85 years from six villages of the island of Krk. "Biological distances" were estimated by the Mahalanobis D2 analysis for bone length (L), total diaphysis width (T) and medullary canal width (M) dimensions of the second left metacarpal bone. Analysis of the osteometric dimensions of metacarpal bones as a measure of biological distance between population groups of the island of Krk indicated bio-cultural and socio-cultural events, rather than geographical distances, to be the primary determinants of anthropogenetic structure of today's population groups of the island.     

Ultraviolet sun radiation and incidence of age-related macular degeneration on Croatian Island Rab

This epidemiological study is completed on island Rab, located in North Adriatic Sea. For this study it is important that Adriatic Sea has one of the highest solar radiations in geographical area of Europe. The aim of this epidemiological study is to estimate correlation between incidence of Age-Related Macular Degeneration (AMD) and exposure of sunlight in two different populations on island Rab. In the first group of population of island Rab, agriculturists and fishermen (n = 1300), incidence of AMD was in 18%, but in urban population only 2.5%. It is very interesting that correlation exists between incidence of AMD and exfoliation syndrome. In the group of chronic exposure to sunlight (agriculturists and fishermen) exfoliation syndrome exists in 28%, but in urban population it has never been seen. The age in both populations was 45-65 years. We can conclude that there is a very significant correlation between chronic exposure to sunlight and appearance of AMD.     

Early colonisation population structure of a Norway rat island invasion

Colonists undergo non-equilibrium processes such as founder effects, inbreeding and changing population size which influence the mating system and demography of a population. Understanding these processes in colonising populations informs management and helps prevent further invasions. We sampled and genotyped most individuals of a Norway rat (Rattus norvegicus) reinvasion on Moturemu island (5 ha) in New Zealand. Population size was most likely between 30 and 33 rats. Genetic methods detected a clear bottleneck signal from the founding population. Parentage assignment revealed promiscuous mating dominated by a few individuals with increasing inbreeding, both putatively a result of small island size. Combining ecological and genetic data from a single sample allowed inferences on population structure and functioning. Invading Norway rats rapidly achieve population structure similar to established island populations despite a small number of colonists and associated inbreeding. Overcoming these initial obstacles to population establishment contributes to the global success of invasive rats.     

Historical processes and biological structure of the populations. Example from the Island of Korcula

The importance of geographical distance as a determining factor of the population's biological and socio-cultural structure was studied on the island of Korcula, Yugoslavia. Migrational kinship coefficients, biological and linguistic distances were analysed in respect to isolation by distance, using Malecot's model. The fit of the model is highly significant for migrational kinship, linguistic, anthropometrical and physiological distances, while for morphometrical distances of metacarpal bones and dermatoglyphic distances, it is not adequate. The major conclusions reached through this analysis are in concordance with the known historical events in the entire region.     

Structural basis for recruitment of RILP by small GTPase Rab7

Rab7 regulates vesicle traffic from early to late endosomes, and from late endosomes to lysosomes. The crystal structure of Rab7-GTP in complex with the Rab7 binding domain of RILP reveals that Rab7 interacts with RILP specifically via two distinct areas, with the first one involving the switch and interswitch regions and the second one consisting of RabSF1 and RabSF4. Disruption of these interactions by mutations abrogates late endosomal/lysosomal targeting of Rab7 and RILP. The Rab7 binding domain of RILP forms a coiled-coil homodimer with two symmetric surfaces to interact with two separate Rab7-GTP molecules, forming a dyad configuration of Rab7-RILP(2)-Rab7. Mutations that disrupt RILP dimerization also abolish its interactions with Rab7-GTP and late endosomal/lysosomal targeting, suggesting that the dimeric form of RILP is a functional unit. Structural comparison suggests that the combined use of RabSF1 and RabSF4 with the switch regions may be a general mode of action for most Rab proteins in regulating membrane trafficking.     

Cancer incidence in eastern Adriatic isolates, Croatia: examples from the islands of Krk, Cres, Losinj, Rab and Pag

As an extension of previous research this study investigates the incidence of cancer in five genetic isolate island populations of the Eastern Adriatic, Croatia. Thorough anthropological research over the past three decades has established some of those populations as outstanding examples of genetic isolates. A previous study which found higher cancer incidence in 5 Eastern Adriatic islands than in a control population supported a hypothesis that among the founders of these populations there were genetic variants (especially with recessive inheritance) responsible for genetic susceptibility to certain types of cancer. This study sought to investigate cancer incidence in 5 further island populations. All cancer cases in five island populations (Krk, Cres, Losinj, Rab and Pag) over the 20-year period (1971 to 1990) was extracted from the data of the Croatian Cancer Registry. The mainland populations of Istrian and Primorsko-Goranska County, characterized by similar environmental factors but an outbred genetic structure, represented a control population. After standardization by by sex and age, cancer incidence was higher in the island populations than in the control population in both sexes. The cancer sites primarily responsible for the excess incidence were prostate, stomach and pancreatic cancer in males, and ovarian, breast, stomach, bowel, and brain cancer in females. The reasons for the increased cancer incidence are uncertain and may be due to different environmental exposure between the two populations. However, it is possible that genetic isolation and inbreeding are important factors. Further investigations of cancer in these isolate populations are warranted to explore these findings further.     

Sunlight and incidence of pterygium on Croatian Island Rab--epidemiological study

The aim of this epidemiologic study, on small island Rab, in North Adriatic Sea, is to estimate correlation between climatic factors, specially chronic exposure to strong visible and UV light, and appearance of pterygium and exfoliation syndrome. In the first group of population which live in a village and who are agriculturists and fishermen (480 persons) appearance of pterygium is in 23% (16% in males and 7% in females), but 0.0% in urban people (61 people). The appearance of exfoliation syndrome was in the first group of agriculturists and fishermen population in 21%, of which 19% of males and 2% of females, and in urban people 0.0%. The higher intraocular pressure in exfoliation syndrome was 92%. All population in this examination were in the highest age (mean age is 65-80 years). Chronic exposure to sunlight caused the high percentage appearance of pterygium and exfoliation syndrome.     

Rab27a regulates exocytosis of tertiary and specific granules in human neutrophils

The correct mobilization of cytoplasmic granules is essential for the proper functioning of human neutrophils in host defense and inflammation. In this study, we have found that human peripheral blood neutrophils expressed high levels of Rab27a, whereas Rab27b expression was much lower. This indicates that Rab27a is the predominant Rab27 isoform present in human neutrophils. Rab27a was up-regulated during neutrophil differentiation of HL-60 cells. Subcellular fractionation and immunoelectron microscopy studies of resting human neutrophils showed that Rab27a was mainly located in the membranes of specific and gelatinase-enriched tertiary granules, with a minor localization in azurophil granules. Rab27a was largely absent from CD35-enriched secretory vesicles. Tertiary and specific granule-located Rab27a population was translocated to the cell surface upon neutrophil activation with PMA that induced exocytosis of both tertiary and specific granules. Specific Abs against Rab27a inhibited Ca(2+) and GTP-gamma-S activation and PMA-induced exocytosis of CD66b-enriched tertiary and specific granules in electropermeabilized neutrophils, whereas secretion of CD63-enriched azurophil granules was scarcely affected. Human neutrophils lacked or expressed low levels of most Slp/Slac2 proteins, putative Rab27 effectors, suggesting that additional proteins should act as Rab27a effectors in human neutrophils. Our data indicate that Rab27a is a major component of the exocytic machinery of human neutrophils, modulating the secretion of tertiary and specific granules that are readily mobilized upon neutrophil activation.     

Proteomics of photoreceptor outer segments identifies a subset of SNARE and Rab proteins implicated in membrane vesicle trafficking and fusion

The outer segment is a specialized compartment of vertebrate rod and cone photoreceptor cells where phototransduction takes place. In rod cells it consists of an organized stack of disks enclosed by a separate plasma membrane. Although most proteins involved in phototransduction have been identified and characterized, little is known about the proteins that are responsible for outer segment structure and renewal. In this study we used a tandem mass spectrometry-based proteomics approach to identify proteins in rod outer segment preparations as an initial step in defining their roles in photoreceptor structure, function, renewal, and degeneration. Five hundred and sixteen proteins were identified including 41 proteins that function in rod and cone phototransduction and the visual cycle and most proteins previously shown to be involved in outer segment structure and metabolic pathways. In addition, numerous proteins were detected that have not been previously reported to be present in outer segments including a subset of Rab and SNARE proteins implicated in vesicle trafficking and membrane fusion. Western blotting and immunofluorescence microscopy confirmed the presence of Rab 11b, Rab 18, Rab 1b, and Rab GDP dissociation inhibitor in outer segments. The SNARE proteins, VAMP2/3, syntaxin 3, N-ethylmaleimide-sensitive factor, and Munc 18 detected in outer segment preparations by mass spectrometry and Western blotting were also observed in outer segments by immunofluorescence microscopy. Syntaxin 3 and N-ethylmaleimide- sensitive factor had a restricted localization at the base of the outer segments, whereas VAMP2/3 and Munc 18 were distributed throughout the outer segments. These results suggest that Rab and SNARE proteins play a role in vesicle trafficking and membrane fusion as part of the outer segment renewal process. The data set generated in this study is a valuable resource for further analysis of photoreceptor outer segment structure and function.     

Crystal structure of rab11 in complex with rab11 family interacting protein 2

The small GTPase Rab11 regulates the recycling of endosomes to the plasma membrane via interactions with the Rab11 family of interacting proteins (FIPs). FIPs contain a highly conserved Rab binding domain (RBD) at their C termini whose structure is unknown. Here, we have determined the crystal structure of the RBD of FIP2 in complex with Rab11(GTP) by single wavelength anomalous diffraction methods. The overall structure is a heterotetramer with dyad symmetry, arranged as a Rab11-(FIP2)2-Rab11 complex. FIP2 forms a central alpha-helical coiled coil, with both helices contributing to the Rab11 binding patch on equivalent and opposite sides of the homodimer. Switch 1 of Rab11 is embedded between the two helices, while switch 2 remains flexible and is peripherally associated with the effector. The complex reveals the structural basis for Rab11 recognition by FIPs and suggests the molecular mechanisms underlying endocytic recycling pathways.     

Rab41 Is a Novel Regulator of Golgi Apparatus Organization That Is Needed for ER-To-Golgi Trafficking and Cell Growth

Background

The 60⁺ members of the mammalian Rab protein family group into subfamilies postulated to share common functionality. The Rab VI subfamily contains 5 Rab proteins, Rab6a/a’, Rab6b, Rab6c and Rab41. High-level knockdown of Rab6a/a’ has little effect on the tightly organized Golgi ribbon in HeLa cells as seen by fluorescence microscopy. In striking contrast, we found Rab41 was strongly required for normal Golgi ribbon organization.

Methods/Results

Treatment of HeLa cells with Rab41 siRNAs scattered the Golgi ribbon into clustered, punctate Golgi elements. Overexpression of GDP-locked Rab41, but not wild type or GTP-locked Rab41, produced a similar Golgi phenotype. By electron microscopy, Rab41 depletion produced short, isolated Golgi stacks. Golgi-associated vesicles accumulated. At low expression levels, wild type and GTP-locked Rab41 showed little concentration in the Golgi region, but puncta were observed and most were in ruffled regions at the cell periphery. There was 25% co-localization of GTP-locked Rab41 with the ER marker, Sec61p. GDP-locked Rab41, as expected, displayed an entirely diffuse cytoplasmic distribution. Depletion of Rab41 or overexpression of GDP-locked Rab41 partially inhibited ER-to-Golgi transport of VSV-G protein. However, Rab41 knockdown had little, if any, effect on endosome-to-Golgi transport of SLTB. Additionally, after a 2-day delay, treatment with Rab41 siRNA inhibited cell growth, while overexpression of GDP-locked Rab41, but not wild type or GTP-locked Rab41, produced a rapid, progressive cell loss. In double knockdown experiments with Rab6, the Golgi ribbon was fragmented, a result consistent with Rab41 and Rab6 acting in parallel.

Conclusion

We provide the first evidence for distinctive Rab41 effects on Golgi organization, ER-to-Golgi trafficking and cell growth. When combined with the evidence that Rab6a/a’ and Rab6b have diverse roles in Golgi function, while Rab6c regulates mitotic function, our data indicate that Rab VI subfamily members, although related by homology and structure, share limited functional conservation.     

Genetic structure of the Canarian palm tree (Phoenix canariensis) at the island scale: does the ‘island within islands’ concept apply to species with high colonisation ability?

• Oceanic islands are dynamic settings that often promote within‐island patterns of strong population differentiation. Species with high colonisation abilities, however, are less likely to be affected by genetic barriers, but island size may impact on species genetic structure regardless of dispersal ability.
• The aim of the present study was to identify the patterns and factors responsible for the structure of genetic diversity at the island scale in Phoenix canariensis, a palm species with high dispersal potential. To this end, we conducted extensive population sampling on the three Canary Islands where the species is more abundant and assessed patterns of genetic variation at eight microsatellite loci, considering different within‐island scales.
• Our analyses revealed significant genetic structure on each of the three islands analysed, but the patterns and level of structure differed greatly among islands. Thus, genetic differentiation fitted an isolation‐by‐distance pattern on islands with high population densities (La Gomera and Gran Canaria), but such a pattern was not found on Tenerife due to strong isolation between colonised areas. In addition, we found a positive correlation between population geographic isolation and fine‐scale genetic structure.
• This study highlights that island size is not necessarily a factor causing strong population differentiation on large islands, whereas high colonisation ability does not always promote genetic connectivity among neighbouring populations. The spatial distribution of populations (i.e. landscape occupancy) can thus be a more important driver of plant genetic structure than other island, or species′ life‐history attributes.

     

Genetic epidemiological studies of eastern Adriatic Island isolates, Croatia: objective and strategies

In this paper, the authors discuss why isolate island populations represent a particularly helpful model for genetic epidemiological studies. A thorough previous anthropological research carried out in Eastern Adriatic island isolates, Croatia, in terms of ethnohistory, geography and current demography is reviewed. The major results of the studies of population genetic structure of those populations, including model-bound and model-free approaches, the analyses of serogenetic polymorphisms and most recent studies using HLA class II, VNTR and STR DNA polymorphisms, are briefly presented. The organization of health care on the islands is analyzed and some relevant details of specific medical problems and some autochtonous diseases in these island populations is noted. The authors present in outline four illustrative examples of research opportunities which are afforded by the unique circumstances found in these isolate communities. These relate to hereditary dwarfism on Krk island, Mal de Meleda on Mljet island, extreme inbreeding on Susak island and population genetics of cancer on the islands of Brac, Hvar, Korcula, Vis and Lastovo. Finally, the authors develop objectives and strategies for a long-term genetic epidemiological research of these populations and suggest that such a programme of investigation would further our understanding of the causes of (rare) diseases which are uniquely important to these communities but also of common diseases which are important contributors to the burden of disease both in these islands and throughout the world.     

Y-chromosome based evidence for pre-neolithic origin of the genetically homogeneous but diverse Sardinian population: inference for association scans

The island of Sardinia shows a unique high incidence of several autoimmune diseases with multifactorial inheritance, particularly type 1 diabetes and multiple sclerosis. The prior knowledge of the genetic structure of this population is fundamental to establish the optimal design for association studies in these diseases. Previous work suggested that the Sardinians are a relatively homogenous population, but some reports were contradictory and data were largely based on variants subject to selection. For an unbiased assessment of genetic structure, we studied a combination of neutral Y-chromosome variants, 21 biallelic and 8 short tandem repeats (STRs) in 930 Sardinian males. We found a high degree of interindividual variation but a homogenous distribution of the detected variability in samples from three separate regions of the island. One haplogroup, I-M26, is rare or absent outside Sardinia and is very common (0.37 frequency) throughout the island, consistent with a founder effect. A Bayesian full likelihood analysis (BATWING) indicated that the time from the most recent common ancestor (TMRCA) of I-M26, was 21.0 (16.0-25.5) thousand years ago (KYA) and that the population began to expand 14.0 (7.8-22.0) KYA. These results suggest a largely pre-Neolithic settlement of the island with little subsequent gene flow from outside populations. Consequently, Sardinia is an especially attractive venue for case-control genome wide association scans in common multifactorial diseases. Concomitantly, the high degree of interindividual variation in the current population facilitates fine mapping efforts to pinpoint the aetiologic polymorphisms.     

Regulation of autophagy by the Rab GTPase network

Autophagy (macroautophagy) is a highly conserved intracellular and lysosome-dependent degradation process in which autophagic substrates are enclosed and degraded by a double-membrane vesicular structure in a continuous and dynamic vesicle transport process. The Rab protein is a small GTPase that belongs to the Ras-like GTPase superfamily and regulates the vesicle traffic process. Numerous Rab proteins have been shown to be involved in various stages of autophagy. Rab1, Rab5, Rab7, Rab9A, Rab11, Rab23, Rab32, and Rab33B participate in autophagosome formation, whereas Rab9 is required in non-canonical autophagy. Rab7, Rab8B, and Rab24 have a key role in autophagosome maturation. Rab8A and Rab25 are also involved in autophagy, but their role is unknown. Here, we summarize new findings regarding the involvement of Rabs in autophagy and provide insights regarding future research on the mechanisms of autophagy regulation.     

Fine-scale population genetic structure of a wildlife disease vector: the southern house mosquito on the island of Hawaii

The southern house mosquito, Culex quinquefasciatus, is a widespread tropical and subtropical disease vector. In the Hawaiian Islands, where it was introduced accidentally almost two centuries ago, it is considered the primary vector of avian malaria and pox. Avian malaria in particular has contributed to the extinction and endangerment of Hawaii's native avifauna, and has altered the altitudinal distribution of native bird populations. We examined the population genetic structure of Cx. quinquefasciatus on the island of Hawaii at a smaller spatial scale than has previously been attempted, with particular emphasis on the effects of elevation on population genetic structure. We found significant genetic differentiation among populations and patterns of isolation by distance within the island. Elevation per se did not have a limiting effect on gene flow; however, there was significantly lower genetic diversity among populations at mid elevations compared to those at low elevations. A recent sample taken from just above the predicted upper altitudinal distribution of Cx. quinquefasciatus on the island of Hawaii was confirmed as being a temporary summer population and appeared to consist of individuals from more than one source population. Our results indicate effects of elevation gradients on genetic structure that are consistent with known effects of elevation on population dynamics of this disease vector.     

Pine reforestation of degraded sites on the island of Rab,Croatia

Abstract

Degradation of forest sites on the island of Rab goes back several hundred years. The causes include in the first place negative anthropogenic impacts, followed by climatic conditions that are hostile to natural regeneration of climatozonal vegetation. In a part of the island, devastation has led to the disappearance of forests or the preservation of only degraded forms of the basic autochthonous forest vegetation, the forest of holm oak and manna ash (Fraxino orni‐Quercetum ilicis H‐ic/1956/1958). The beginning of the twentieth century saw intensive reforestation activities aimed at halting site degradation processes. The main task of the pines was to create site conditions for the return of climatozonal vegetation. The paper examines the correlation between pine cultures and the return of autochthonous vegetation. Differences were found among forest cultures of maritime (Pinus pinaster Aiton), black (Pinus nigra J.F.Arnold) and Aleppo pine (Pinus halepensis L.). Moreover, the results confirm the justifiability of reforesting degraded sites with pines, but they also reveal the absence of more pronounced effects on the sites. Today, there are about 1000 hectares of pine cultures on the island of Rab, yet climatozonal vegetation has been re‐established in only a small part of these forest cultures.