Ethnobiological notes on the Khasi and Garo tribes of Meghalaya,Northeast India

A total of 105 plants used for food and medicine and 11 animals hunted and gathered for meat by the Khasis and Garos of Meghalaya were identified. Of the total plants recorded, 85 were used by the Garos alone, only three by the Khasis whereas the other 17 were used by both tribes. In addition to fresh use in-season many plant products were processed for storage and use off-season. Although all adults were familiar with various uses of plants and animals, the village elders were more knowledgeable. Garos have especially knowledgeable curers. Wild foods are of particular value for tiding over lean periods when resources from agriculture and animal husbandry systems are scarce, especially for the poorer sections of society. The importance of recording the use of plants and animals in this region is especially important because of rapid loss of rain forest habitats.     

The missing link between hydrogenosomes and mitochondria

Mitochondria typically respire oxygen and possess a small DNA genome. But among various groups of oxygen-shunning eukaryotes, typical mitochondria are often lacking, organelles called hydrogenosomes being found instead. Like mitochondria, hydrogenosomes are surrounded by a double-membrane, produce ATP and sometimes even have cristae. In contrast to mitochondria, hydrogenosomes produce molecular hydrogen through fermentations, lack cytochromes and usually lack DNA. Hydrogenosomes do not fit into the conceptual mold cast by the classical endosymbiont hypothesis about the nature of mitochondria. Accordingly, ideas about their evolutionary origins have focussed on the differences between the two organelles instead of their commonalities. Are hydrogenosomes fundamentally different from mitochondria, the result of a different endosymbiosis? Or are our concepts about the mitochondrial archetype simply too narrow? A new report has uncovered DNA in the hydrogenosomes of anaerobic ciliates. The sequences show that these hydrogenosomes are, without a doubt, mitochondria in the evolutionary sense, even though they differ from typical mitochondria in various biochemical properties. The new findings are a benchmark for our understanding of hydrogenosome origins.     

Regional Maritime Regime Building: Prospects in Northeast and Southeast Asia

Maritime issues are rising to the forefront of Asian security concerns. But maritime management regimes can constrain conflict and create confidence in co-operation. Such regimes can define the range of permissible state behavior and resolve dilemmas stemming from the sharing of common resources. Regimes originate through imposition, spontaneous processes, or negotiation and are supplied when there is sufficient demand for the functions they perform. Integrative forces that support regime formation are the existence of other international arrangements in the region; ethnic, cultural, or historical interstate relationships; and clear indications of benefits to be gained. Often a shock or crisis enhances regime formation or its robustness. Disintegrative forces include political or territorial differences, competition for leadership, and opposition to regionalism. In regional co-operation on maritime issues, Southeast Asia is clearly more advanced than Northeast Asia. However, the absence of robust multilateral maritime regimes in Asia reflects state perceptions that the costs outweigh the benefits. The primacy of dis-integrative factors argues strongly for an ad hoc, issue-specific, evolutionary process for multilateral maritime regime building in Asia.     

An interaction between human Sec63 and nucleoredoxin may provide the missing link between the SEC63 gene and polycystic liver disease

The formation of multiple cysts in one or several organs is a characteristic of several human inherited diseases. Recent research suggests that problems in planar cell polarity may be the common denominator in polycystic diseases. Mutations in at least two genes are linked to autosomal dominant polycystic liver disease (PCLD), PRKCSH and SEC63. A recent study linked PRKCSH to the signaling- and cytoskeletal adaptor-component β-catenin. In a yeast two hybrid screen we identified the cytosolic protein nucleoredoxin (NRX) as an interaction partner of human Sec63. Since NRX is involved in the Wnt signaling pathways, we characterized this interaction. Thus, Sec63 is linked to the Wnt signaling pathways and this interaction may be the reason why mutations in SEC63 can lead to PCLD.

Structured summary

Sec63physically interacts with NRX by two hybrid(View interaction)NRXbinds to Sec63 by peptide array (View Interaction 1, 2)Sec63binds to NRX by pull down(View interaction)Sec63binds to NRX by peptide array (View Interaction 1, 2, 3)     

A hitherto unknown hybridization between Chilean and South Polar skua

 Three skua specimens with a colouration pattern of the Chilean skua were observed at Potter Peninsula, King George Island, Antarctica. Two of these were breeding birds. However, they showed a pattern of mitochondrial DNA typical for South Polar skua. These birds thus represent hybrids originating from male Chilean skua. The third bird could not be caught. It appeared to be indistinguishable from Chilean skua. Received: 9 October 1995/Accepted: 17 March 1996     

A microsatellite study to disentangle the ambiguity of linguistic,geographic, ethnic and genetic influences on tribes of India to get a better clarity of the antiquity and peopling of South Asia

An understanding of the genetic affinity and the past history of the tribal populations of India requires the untangling of the confounding influences of language, ethnicity, and geography on the extant diverse tribes. The present study examines the genetic relationship of linguistically (Dravidian, Austro‐Asiatic, and Tibeto‐Burman) and ethnically (Australian and East Asian) diverse tribal populations (46) inhabiting different regions of the Indian subcontinent. For the purpose, we have utilized the published data on allele frequency of 15 autosomal STR loci of our study on six Adi sub‐tribes of Arunachal Pradesh and compared the same with the reported allele frequency data, for nine common autosomal STR loci, of 40 other tribes. Phylogenetic and principal component analyses exhibit geography based clustering of Tibeto‐Burman speakers and separation of the Mundari and Mon‐Khmer speaking Austro‐Asiatic populations. The combined analyses of all 46 populations show clustering of the groups belonging to same ethnicity and inhabiting contiguous geographic regions, irrespective of their different languages. These results help us to reconstruct and understand three plausible scenarios of the antiquity of Indian tribal populations: the Dravidian and Austro‐Asiatic (Mundari) tribes were possibly derived from common early settlers; the Tibeto‐Burman tribes possibly belonged to a different ancestry and the Mon‐Khmer speaking Austro‐Asiatic populations share a common ancestry with some of the Tibeto‐Burman speakers. Am J Phys Anthropol, 2009. © 2009 Wiley‐Liss, Inc.     

The missing link between neurobiology and behavior in Aplysia conditioning

Over the past decades, a wealth of findings has led to a substantial change in the assumed complexity of classical conditioning. The combined evidence indicates that temporal pairing is neither necessary nor sufficient for the formation of an associative connection. At the same time, studies of model invertebrate nervous systems have allowed us to ask a series of questions about the molecular basis of associative conditioning. The discovery of a pairing-sensitive mechanism in the gill-withdrawal circuitry of Aplysia is regarded as the hallmark of the reductionist approach. This review outlines the insights gathered from behavioral and neurobiological studies. Furthermore, the conceptual frameworks guiding research at the ‘what’ and ‘how’ levels of analysis are compared and contrasted. I argue that a rich cognitive view of conditioning has emerged at the ‘what’ level, whereas the traditional notion of temporal pairing still drives research at the ‘how’ level. A complete account of classical conditioning has to await the resolving of this discordance.     

Ethnogenesis of South Asia with special reference to India

An attempt has been made to illustrate the quite complicated process of ethnogenesis in South Asia from the viewpoint of physical anthropology. The numerous invading waves which reached the Indian subcontinent from the northwest played an important role in this process. Most important for the ethnogenesis of South Asia was the invasion of Indo-Aryan groups in the middle of the 2nd millenium B.C. known from historical sources. In large parts of the Indo-Pakistan region they assimilated the aboriginal population in ethnic, cultural and linguistic respects in the course of time. Furthermore, the ethnogenesis of the Indian region is determined by the caste system of Hinduism which, however, is not as rigid as generally assumed. There are numerous evidences that since more than 2000 years a slow but steady process of assimilation and integration of tribal groups, living in the forest areas of Central India, into the Hindu caste system took place, a process which is still going on. It is intended to demonstrate to what degree the ethnogenetic processes in South Asia, known from prehistoric and historical sources, can be traced in human skeletal findings of different time periods as well as in the anthropological structure of the living population. Finally, hypotheses and theories, especially those of Risley and von Eickstedt are discussed, who attempted to interpret the great variability of anthropological and morphological traits in the Indian subcontinent by taking into consideration the existence of different old population substrata and their mixing and assimilation.     

The missing link between envelope formation and fusion in alphaviruses.

Recent structural analyses of the Semliki Forest virus envelope suggest that the spike subunit E1, which is responsible for virus membrane fusion, also maintains the organization of the spike protein shell that encompasses the enveloped virus. This gives E1 a unique opportunity to control membrane stability during the membrane fusion reaction. Here, we present a model for this control mechanism.     

The vesicular ATPase: A missing link between acidification and exocytosis

The vesicular adenosine triphosphatase (ATPase) acidifies intracellular compartments, including synaptic vesicles and secretory granules. A controversy about a second function of this ATPase in exocytosis has been fuelled by questions about multiple putative roles of acidification in the exocytic process. Now, Poëa-Guyon et al. (2013. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201303104) present new evidence that the vesicular ATPase performs separate acidification and exocytosis roles and propose a mechanism for how these two functions are causally linked.Vesicular H⁺-ATPases (V-ATPases) function as ATP-driven proton pumps in intracellular compartments, such as endosomes, Golgi-derived vesicles, secretory vesicles, synaptic vesicles, lysosomes, and vacuoles (Forgac, 2007). Acidification is important for a plethora of cell biological processes ranging from endosomal ligand–receptor dissociation to lysosomal degradation (Yan et al., 2009; Williamson et al., 2010; Zoncu et al., 2011). Consequently, interfering with V-ATPase function leads to direct and indirect defects that are difficult to tease apart. In addition, acidification-independent roles of the V-ATPase in secretion and membrane fusion have been proposed (Israël et al., 1986; Peters et al., 2001; Morel et al., 2003; Hiesinger et al., 2005; Liégeois et al., 2006; Sun-Wada et al., 2006; Peri and Nüsslein-Volhard, 2008). The difficulty to distinguish consequences of an acidification-independent mechanism from indirect effects of acidification defects is exacerbated by an unclear dependence of secretion on acidification (Cousin and Nicholls, 1997; Ungermann et al., 1999; Hiesinger et al., 2005).In synaptic vesicles, the V-ATPase generates a proton gradient that is used by an antiporter to fill synaptic vesicles with neurotransmitter. Hence, loss of acidification leads to “empty” synaptic vesicles and loss of neurotransmitter release. Can such vesicles still fuse and thereby “shoot blanks”? The V-ATPase comprises of two sectors that can reversibly dissociate: the cytosolic V1 sector and the membrane-bound V0 sector. Loss of the neuronal a1 subunit of the V0 sector (V0a1) leads to almost complete loss of neurotransmission in Drosophila melanogaster—a phenotype that may result from a defect in neurotransmitter loading or exocytosis (Hiesinger et al., 2005). Single vesicle release events in the V0a1 mutant revealed a quantal postsynaptic response, suggesting that at least some vesicles are loaded. In addition, loss of V0a1 impairs synaptic vesicle cycling in an FM1-43 dye uptake assay, whereas pharmacological block of the V-ATPase with bafilomycin causes no significant defect in this assay (Hiesinger et al., 2005). These findings supported previous studies of an acidification-independent role of the yeast V0 sector and specifically the V0a1 orthologue vph1 in vacuole fusion (Peters et al., 2001; Bayer et al., 2003). They also support earlier controversial implications of the V-ATPase V0 sector in neurotransmitter release (Israël et al., 1986). More recently, numerous studies have added evidence in worm, fish, fly, and mouse for possible acidification-independent roles of various V-ATPase V0 subunits in secretion or membrane fusion (Bayer et al., 2003; Lee et al., 2006; Liégeois et al., 2006; Sun-Wada et al., 2006; Peri and Nüsslein-Volhard, 2008; Di Giovanni et al., 2010; Williamson et al., 2010; Strasser et al., 2011). However, questions about the relationship of V-ATPase–dependent acidification and the observed secretion or membrane fusion defects remained. How can one cleanly separate between two protein functions if one potentially depends on the other? The study of V0a1 has been complicated by the finding that it is not only a synaptic vesicle protein but also localizes to other organelles. Consequently, specific disruption of the acidification function of V0a1 led to endolysosomal acidification defects, even though it partially restored neurotransmission (Williamson et al., 2010). A better dissection of the two possible functions is needed.In this issue of JCB, Poëa-Guyon et al. provide compelling evidence for two separable functions of V0a1 in acidification and exocytosis. Instead of a genetic dissection, they opted for an elegant temporal dissection with the idea that acute inactivation of a function of V0a1 in exocytosis should instantly block neurotransmission, whereas acute inactivation of the proton pump should leave neurotransmission functional as long as loaded vesicles are available. Indeed, Poëa-Guyon et al. (2013) found a fast disruption of secretion in both primary rat neuronal culture and chromaffin cells when they acutely inactivated V0a1 using chromophore-assisted light inactivation. In contrast, inactivation of the reversibly associated V1 sector revealed very different effects than what would be expected from a loss of the proton pump.How about the dependence of exocytosis on acidification? Poëa-Guyon et al. (2013) developed an assay based on granule exocytosis in neurosecretory PC12 cells. Compartmental proton gradients can be abolished by a variety of means, including pharmacological inhibition of the V-ATPase with bafilomycin or concanamycin. A more acute destruction of intracompartmental proton gradients can be achieved through addition of alkalizing ammonium chloride or the potassium ionophore nigericin, which exchanges intracompartmental protons with potassium ions. Interestingly, Poëa-Guyon et al. (2013) found that only the acute disruption of the intracompartmental proton gradients with ammonium chloride or nigericin leads to an impairment of secretion but not block of the V-ATPase. What happens to the V-ATPase and its acidification-independent function under these different conditions? The authors show that both ammonium chloride and nigericin not only abolish the proton gradient but also lead to increased association of the V0 and V1 sectors (Fig. 1). This association is required to form a functional pump. A straightforward explanation for this observation is that the cell attempts to activate the proton pump to reacidify vesicles that lost their proton gradient. In contrast, the pharmacological block of the V-ATPase itself leads to increased free V0 sectors, consistent with loss of proton pump function. In a key experiment, Poëa-Guyon et al. (2013) show that this pharmacological inhibition of the V-ATPase with bafilomycin can override the effects of ammonium chloride or nigericin and restore secretion. If the pharmacological block of the V-ATPase prevents V0–V1 association, no functional pumps assemble even in the presence of ammonium chloride or nigericin. This result implies that the V0–V1 association itself prevents exocytosis. Pharmacological V0–V1 dissociation seems sufficient to expose V0 and exert a V1-independent function in exocytosis. This conclusion is consistent with previous findings in which the same pharmacological inhibition of the V-ATPase was found to leave exocytosis and endocytosis intact (Cousin and Nicholls, 1997; Hiesinger et al., 2005). However, the interpretation of the data changes: according to the new findings, exocytosis does not depend on vesicle acidification, per se, but on V0–V1 association that results from lack of acidification. Acidification and V-ATPase assembly thereby become a checkpoint for vesicle loading, and the assembled V-ATPase becomes a no-go signal for fusion (Fig. 1). The model is elegant and leads Poëa-Guyon et al. (2013) to suggest the V-ATPase as an acidification sensor, similar to previous observations (Hurtado-Lorenzo et al., 2006). However, whether it is really the V-ATPase itself that senses the proton gradient is not directly assessed in this study.Open in a separate windowFigure 1.V-ATPase V0–V1 association blocks secretion. (A) Poëa-Guyon et al. (2013) suggest that dissociation of V0 (red boxes) and V1 (green cylinders) sectors follows vesicle acidification (yellow) and frees the V0 sector for an acute, acidification-independent function in secretion.(B) V-ATPase–independent pharmacological disruption of vesicular acidification causes increased V0–V1 assembly of the functional proton pump, which in turn blocks secretion.(C) Pharmacological disruption of the V-ATPase disrupts both vesicle acidification and V0–V1 assembly, thereby permitting V0-dependent secretion. This mechanism can override disruption of acidification shown in B and restores secretion of nonacidified vesicles.How general is the V-ATPase checkpoint, and what is the mechanism of V0-mediated, acidification-independent exocytosis? Both questions remain unanswered. The checkpoint idea is beautiful and does not obviously contradict current ideas on exocytic regulation. However, potential mechanisms for V0-mediated membrane fusion remain controversial (Saw et al., 2011; Ernstrom et al., 2012). In yeast, V0 proteolipid expansion in the membrane has been proposed to play a direct role in lipid mixing during vacuole fusion based on a thorough genetic dissection of fusion and acidification functions of the V0 sector (Strasser et al., 2011). No such role has hitherto been shown for neurotransmitter release, which comprises numerous different forms of vesicle release that are differentially regulated. A better genetic or pharmacological dissection is needed to reveal when, where, and how V0 meddles with membrane fusion.     

Deforestation rates in insular Southeast Asia between 2000 and 2010

Insular Southeast Asia experienced the highest level of deforestation among all humid tropical regions of the world during the 1990s. Owing to the exceptionally high biodiversity in Southeast Asian forest ecosystems and the immense amount of carbon stored in forested peatlands, deforestation in this region has the potential to cause serious global consequences. In this study, we analysed deforestation rates in insular Southeast Asia between 2000 and 2010 utilizing a pair of 250 m spatial resolution land cover maps produced with regional methodology and classification scheme. The results revealed an overall 1.0% yearly decline in forest cover in insular Southeast Asia (including the Indonesian part of New Guinea) with main change trajectories to plantations and secondary vegetation. Throughout the region, peat swamp forests experienced clearly the highest deforestation rates at an average annual rate of 2.2%, while lowland evergreen forests declined by 1.2%/yr. In addition, the analysis showed remarkable spatial variation in deforestation levels within the region and exposed two extreme concentration areas with over 5.0% annual forest loss: the eastern lowlands of Sumatra and the peatlands of Sarawak, Borneo. Both of these areas lost around half of their year 2000 peat swamp forest cover by 2010. As a whole this study has shown that deforestation has continued to take place on high level in insular Southeast Asia since the turn of the millennium. These on‐going changes not only endanger the existence of numerous forest species endemic to this region, but they further increase the elevated carbon emissions from deforested peatlands of insular Southeast Asia thereby directly contributing to the rising carbon dioxide concentration in the atmosphere.     

The missing link between indoleamine 2,3-dioxygenase mediated antibacterial and immunoregulatory effects

The interferon (IFN)–γ-inducible tryptophan degrading enzyme indoleamine 2,3-dioxygenase (IDO) has not only been recognized as a potent antimicrobial effector molecule for the last 25 years but was recently found also to have potent immunoregulatory properties. In this study, we provide evidence that both tryptophan starvation and production of toxic tryptophan metabolites are involved in the immunoregulation mediated by IDO, whereas tryptophan starvation seems to be the only antibacterial effector mechanism. A long-studied controversy in the IDO research field is the seemingly contradictory effect of IDO in the defence against infectious diseases. On the one hand, IFN-γ-induced IDO activity mediates an antimicrobial effect, while at the same time IDO inhibits T-cell proliferation and IFN–γ production. Here, we suggest that both effects, dependent on the threshold for tryptophan, cooperate in a reasonable coherence. We found that the minimum concentration of tryptophan required for bacterial growth is 10-40-fold higher than the minimum concentration necessary for T-cell activation. Therefore, we suggest that during the first phase of infection the IDO-mediated tryptophan depletion has a predominantly antimicrobial effect whereas in the next stage, and with ongoing tryptophan degradation, the minimum threshold concentration of tryptophan for T-cell activation is undercut, resulting in an inhibition of T-cell growth and subsequent IDO activation.     

SpeedScreen: The "missing link" between genomics and lead discovery

SpeedScreen is a novel, label-free, in-solution, affinity-based selection methodology for high-throughput screening (HTS) developed at Novartis Pharma. The SpeedScreen protocol comprises in-solution affinity selection, followed by size exclusion chromatography in combination with microbore-liquid-chromatography/electrospray-ionization mass spectrometry (micro-LC/ESI-MS). The authors describe the basic concept behind assay development, HTS, and data analysis with the SpeedScreen technology. Advantages and limitations of SpeedScreen compared to alternative screening technologies are discussed, and an example is given from a SpeedScreen campaign applying this innovative affinity selection concept in HTS.     

Embryo quality: the missing link between pregnancy sickness and pregnancy outcome

Pregnancy sickness is widespread yet its etiology is poorly understood. It is almost certainly endocrine in origin and most likely a product of placental hormones, with human chorionic gonadotropin being the strongest candidate. It has long been known that greater levels of nausea and vomiting during pregnancy are associated with a lower incidence of spontaneous abortion, yet the causal mechanisms remain unclear. One current popular explanation is that nausea and vomiting during pregnancy is fetoprotective, inducing aversions to foods, especially meat, dairy and seafoods, which may carry toxins, pathogens or mutagens. However, most spontaneous abortions arise from genetic or epigenetic defects that are present at or near conception. Moreover, measurements of human chorionic gonadotropin (hCG) at the time of implantation, particularly its hyperglycosylated isoform, accurately predict subsequent spontaneous abortion. Thus the developmental fate of most embryos is fixed before the onset of the symptoms of pregnancy sickness. An alternative explanation for the link between pregnancy sickness and spontaneous abortion is the embryo quality hypothesis: high quality embryos are both more likely to produce the biochemical antecedents of pregnancy sickness and avoid spontaneous abortion. Recent work has shown that the link between pregnancy sickness and spontaneous abortion grows stronger with maternal age, dramatically so in mothers 35 or older. This reflects the parallel rise in the incidence of autosomal aneuploidies with maternal age. The link between pregnancy sickness and spontaneous abortion exists not because nausea and vomiting during pregnancy is fetoprotective, but because nausea and vomiting is an index of a high quality embryo. Pregnancy sickness is not adaptive per se, but the result of an antagonistic pleiotropy over thyroid function, where embryos use hCG to modulate maternal thyroid hormone production during gestation. Embryos benefit from the thyroid hormone production that is key to neurodevelopment, but produce maternal nausea and vomiting as a by-product. Pregnancy sickness, however, may still serve to protect embryo quality but by a different mechanism that posited under the MEPH. Embryo quality is protected by calibrating the dietary intake of a micronutrient – iodine – critical to neuromotor development. For most humans over most of our evolutionary history, iodine has been in short supply, and iodine deficiency is still the most common source of cognitive impairment across the globe. Thus it is of interest that the food aversions most commonly associated with pregnancy sickness, to meat, dairy and seafoods, are also the chief dietary sources of iodine. There is a further intriguing property about iodine: both too little and too much during early pregnancy are damaging to embryo brain development. Given that pregnancy sickness is closely linked to iodine intake and thyroid function (hypothyroidism is associated with lower levels of nausea and vomiting, hyperthyroidism with more), an obvious interpretation emerges. The previously described link between diet and pregnancy sickness – pregnancy sickness is less likely when plants and particularly corn/maize are the sole food staples – arises not because plant food staples are safe, as previously suggested, but because these foods are iodine poor and may, in addition, be goitrogenic. Pregnancy sickness, which reduces the dietary intake of iodine, is clearly maladaptive under conditions of iodine deficiency and hypothyroidism. Conversely, higher levels of pregnancy sickness induced by hyperthyroidism may protect embryos from the inimical effects of excessive dietary iodine during early gestation by reducing the intake of iodine rich foods.