A Deafness Mechanism of Digenic Cx26 (\u3cem\u3eGJB2\u3c/em\u3e) and Cx30 (\u3cem\u3eGJB6\u3c/em\u3e) Mutations: Reduction of Endocochlear Potential by Impairment of Heterogeneous Gap Junctional Function in the Cochlear Lateral Wall

Digenic Connexin26 (Cx26, GJB2) and Cx30 (GJB6) heterozygous mutations are the second most frequent cause of recessive deafness in humans. However, the underlying deafness mechanism remains unclear. In this study, we created different double Cx26 and Cx30 heterozygous (Cx26+/−/Cx30+/−) mouse models to investigate the underlying pathological changes and deafness mechanism. We found that double Cx26+/−/Cx30+/− heterozygous mice had hearing loss. Endocochlear potential (EP), which is a driving force for hair cells producing auditory receptor current, was reduced. However, unlike Cx26 homozygous knockout (Cx26−/−) mice, the cochlea in Cx26+/−/Cx30+/− mice displayed normal development and had no apparent hair cell degeneration. Gap junctions (GJs) in the cochlea form two independent networks: the epithelial cell GJ network in the organ of Corti and the connective tissue GJ network in the cochlear lateral wall. We further found that double heterozygous deletion of Cx26 and Cx30 in the epithelial cells did not reduce EP and had normal hearing, suggesting that Cx26+/−/Cx30+/− may mainly impair gap junctional functions in the cochlear lateral wall and lead to EP reduction and hearing loss. Most of Cx26 and Cx30 in the cochlear lateral wall co-expressed in the same gap junctional plaques. Moreover, sole Cx26+/− or Cx30+/− heterozygous mice had no hearing loss. These data further suggest that digenic Cx26 and Cx30 mutations may impair heterozygous coupling of Cx26 and Cx30 in the cochlear lateral wall to reduce EP, thereby leading to hearing loss

The Bearded Pig (Sus barbatus)

Status categories 2-3 - the nominate subspecies from Borneo, S. b. barbatus, is still widespread but declining in numbers; the western subspecies from Peninsular Malaysia and Sumatra, S. b. oi, and the eastern subspecies from Palawan and neighboring islands, S. b. ahoenobarbus, are both rare. In Borneo, the dipterocarp forests should be deliberately managed for a variety of non-wood as well as wood outputs, which will benefit bearded pigs if wild meat is one of the outputs required. This action requires a fundamental rethinking of forestry management strategy. Conservation areas need to be maintained, and the communal forest system expanded, thereby retaining intact forest areas for the benefit of rural communities and with them, local bearded pig populations. Detailed, long-term investigation of the behaviour of identified pigs is necessary to resolve outstanding questions of social structure and home range use. In Peninsular or West Malaysia, (northern) Sumatra, Bangka and the Riau Islands, field surveys are needed to correct a lack of information on the distribution and status of S. b. oi and the habitats where they can be expected to survive, which is hampering measures to conserve bearded pigs in these regions. Unlike either of the other two subspecies, these animals are everywhere sympatric with S. scrofa, which may be competitively advantaged by human induced changes in its environment and whose relative abundance may have a negative influence on local attitudes to the management requirements of the rarer form. There is similar lack of recent information on the distribution and status of the Philippine endemic, S. b. ahoenobarbus, which has by far the most restricted range of the three, currently recognized subspecies. The present status of these animals on Balabac is unknown, but they remain quite widely, if patchily, distributed on the Calamian Islands (Busuanga, Culion and Coron) despite intense hunting pressure. Bearded pigs are also reported to be intensively hunted on Palawan, though precise data is lacking on their range there and any future fieldwork on this island is likely to be seriously compromised by the presence of armed rebels. All of these and other related problems are addressed in the proposed action plan for this species, which also recognizes the need to resolve the now rather confused systematic relationships between the three (Sundaic) forms of bearded pigs the closely allied wild pigs of the neighboring Wallacian subregion, i.e. the eastern Philippines' 'philippensis' and 'cebifrons', and the Sulawesi warty pig, S. celebensis

Unfolded states under folding conditions accommodate sequence-specific conformational preferences with random coil-like dimensions

Proteins are marginally stable molecules that fluctuate between folded and unfolded states. Here, we provide a high-resolution description of unfolded states under refolding conditions for the N-terminal domain of the L9 protein (NTL9). We use a combination of time-resolved Förster resonance energy transfer (FRET) based on multiple pairs of minimally perturbing labels, time-resolved small-angle X-ray scattering (SAXS), all-atom simulations, and polymer theory. Upon dilution from high denaturant, the unfolded state undergoes rapid contraction. Although this contraction occurs before the folding transition, the unfolded state remains considerably more expanded than the folded state and accommodates a range of local and nonlocal contacts, including secondary structures and native and nonnative interactions. Paradoxically, despite discernible sequence-specific conformational preferences, the ensemble-averaged properties of unfolded states are consistent with those of canonical random coils, namely polymers in indifferent (theta) solvents. These findings are concordant with theoretical predictions based on coarse-grained models and inferences drawn from single-molecule experiments regarding the sequence-specific scaling behavior of unfolded proteins under folding conditions

Use of sonic tomography to detect and quantify wood decay in living trees.

Premise of the studyField methodology and image analysis protocols using acoustic tomography were developed and evaluated as a tool to estimate the amount of internal decay and damage of living trees, with special attention to tropical rainforest trees with irregular trunk shapes.Methods and resultsLiving trunks of a diversity of tree species in tropical rainforests in the Republic of Panama were scanned using an Argus Electronic PiCUS 3 Sonic Tomograph and evaluated for the amount and patterns of internal decay. A protocol using ImageJ analysis software was used to quantify the proportions of intact and compromised wood. The protocols provide replicable estimates of internal decay and cavities for trees of varying shapes, wood density, and bark thickness.ConclusionsSonic tomography, coupled with image analysis, provides an efficient, noninvasive approach to evaluate decay patterns and structural integrity of even irregularly shaped living trees

Non-L\'evy mobility patterns of Mexican Me'Phaa peasants searching for fuelwood

We measured mobility patterns that describe walking trajectories of individual Me'Phaa peasants searching and collecting fuelwood in the forests of "La Monta\~na de Guerrero" in Mexico. These one-day excursions typically follow a mixed pattern of nearly-constant steps when individuals displace from their homes towards potential collecting sites and a mixed pattern of steps of different lengths when actually searching for fallen wood in the forest. Displacements in the searching phase seem not to be compatible with L\'evy flights described by power-laws with optimal scaling exponents. These findings however can be interpreted in the light of deterministic searching on heavily degraded landscapes where the interaction of the individuals with their scarce environment produces alternative searching strategies than the expected L\'evy flights. These results have important implications for future management and restoration of degraded forests and the improvement of the ecological services they may provide to their inhabitants.Comment: 15 pages, 4 figures. First version submitted to Human Ecology. The final publication will be available at http://www.springerlink.co

Environmental changes and violent conflict

This letter reviews the scientific literature on whether and how environmental changes affect the risk of violent conflict. The available evidence from qualitative case studies indicates that environmental stress can contribute to violent conflict in some specific cases. Results from quantitative large-N studies, however, strongly suggest that we should be careful in drawing general conclusions. Those large-N studies that we regard as the most sophisticated ones obtain results that are not robust to alternative model specifications and, thus, have been debated. This suggests that environmental changes may, under specific circumstances, increase the risk of violent conflict, but not necessarily in a systematic way and unconditionally. Hence there is, to date, no scientific consensus on the impact of environmental changes on violent conflict. This letter also highlights the most important challenges for further research on the subject. One of the key issues is that the effects of environmental changes on violent conflict are likely to be contingent on a set of economic and political conditions that determine adaptation capacity. In the authors' view, the most important indirect effects are likely to lead from environmental changes via economic performance and migration to violent conflict. © 2012 IOP Publishing Ltd

Predicting Future Changes in Muskegon River Watershed Game Fish Distributions under Future Land Cover Alteration and Climate Change Scenarios

Future alterations in land cover and climate are likely to cause substantial changes in the ranges of fish species. Predictive distribution models are an important tool for assessing the probability that these changes will cause increases or decreases in or the extirpation of species. Classification tree models that predict the probability of game fish presence were applied to the streams of the Muskegon River watershed, Michigan. The models were used to study three potential future scenarios: (1) land cover change only, (2) land cover change and a 3°C increase in air temperature by 2100, and (3) land cover change and a 5°C increase in air temperature by 2100. The analysis indicated that the expected change in air temperature and subsequent change in water temperatures would result in the decline of coldwater fish in the Muskegon watershed by the end of the 21st century while cool‐ and warmwater species would significantly increase their ranges. The greatest decline detected was a 90% reduction in the probability that brook trout Salvelinus fontinalis would occur in Bigelow Creek. The greatest increase was a 276% increase in the probability that northern pike Esox lucius would occur in the Middle Branch River. Changes in land cover are expected to cause large changes in a few fish species, such as walleye Sander vitreus and Chinook salmon Oncorhynchus tshawytscha, but not to drive major changes in species composition. Managers can alter stream environmental conditions to maximize the probability that species will reside in particular stream reaches through application of the classification tree models. Such models represent a good way to predict future changes, as they give quantitative estimates of the n‐dimensional niches for particular species.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141570/1/tafs0396.pd

A New Paradigm for Large Earthquakes in Stable Continental Plate Interiors

Large earthquakes within stable continental regions (SCR) show that significant amounts of elastic strain can be released on geological structures far from plate boundary faults, where the vast majority of the Earth's seismic activity takes place. SCR earthquakes show spatial and temporal patterns that differ from those at plate boundaries and occur in regions where tectonic loading rates are negligible. However, in the absence of a more appropriate model, they are traditionally viewed as analogous to their plate boundary counterparts, occuring when the accrual of tectonic stress localized at long-lived active faults reaches failure threshold. Here we argue that SCR earthquakes are better explained by transient perturbations of local stress or fault strength that release elastic energy from a pre-stressed lithosphere. As a result, SCR earthquakes can occur in regions with no previous seismicity and no surface evidence for strain accumulation. They need not repeat, since the tectonic loading rate is close to zero. Therefore, concepts of recurrence time or fault slip rate do not apply. As a consequence, seismic hazard in SCRs is likely more spatially distributed than indicated by paleoearthquakes, current seismicity, or geodetic strain rates

Influence of soluble or matrix-bound isoforms of vascular endothelial growth factor-A on tumor response to vascular-targeted strategies

Antiangiogenic therapy based on blocking the actions of vascular endothelial growth factor-A (VEGF) can lead to "normalization" of blood vessels in both animal and human tumors. Differential expression of VEGF isoforms affects tumor vascular maturity, which could influence the normalization process and response to subsequent treatment. Fibrosarcoma cells expressing only VEGF120 or VEGF188 isoforms were implanted either subcutaneously (s.c.) or in dorsal skin-fold "window" chambers in SCID mice. VEGF120 was associated with vascular fragility and hemorrhage. Tumor-bearing mice were treated with repeat doses of SU5416, an indolinone receptor tyrosine kinase inhibitor with activity against VEGFR-2 and proven preclinical ability to induce tumor vascular normalization. SU5416 reduced vascularization in s.c. implants of both VEGF120 and VEGF188 tumors. However, in the window chamber, SU5416 treatment increased red cell velocity in VEGF120 (representing vascular normalization) but not VEGF188 tumors. SU5416 treatment had no effect on growth or necrosis levels in either tumor type but tended to counteract the increase in interstitial fluid pressure seen with growth of VEGF120 tumors. SU5416 pretreatment resulted in the normally fragile blood vessels in VEGF120-expressing tumors becoming resistant to the vascular damaging effects of the tubulin-binding vascular disrupting agent (VDA), combretastatin A4 3-O-phosphate (CA4P). Thus, vascular normalization induced by antiangiogenic treatment can reduce the efficacy of subsequent VDA treatment. Expression of VEGF120 made tumors particularly susceptible to vascular normalization by SU5416, which in turn made them resistant to CA4P. Therefore, VEGF isoform expression may be useful for predicting response to both antiangiogenic and vascular-disrupting therapy