Topical Nutrients Promote Engraftment and Inhibit Wound Contraction of Cultured Skin Substitutes in Athymic Mice

Routine treatment of burns with cultured skin substitutes (CSS) has been limited by poor engraftment and by scarring. Hypothetically, topical application of essential nutrients and/or growth factors may support epithelial survival temporarily during graft vascularization, CSS, composed of human epidermal keratinocytes and dermal fibroblasts attached to collagen-glycosaminoglycan substrates, were incubated for 19 d in media optimized for keratinocytes. CSS, human xenografts, murine autografts, or no grafts were applied orthotopically to full-thickness skin wounds (2 × 2 cm) in athymic mice. Wounds were irrigated for 14 d with 1 ml/d modified cell culture medium or with saline containing epidermal growth factor, or were treated with dry dressings. After 6 weeks, treated sites were scored for percentage original wound area (mean ± SEM) and percentage HLA- ABC-positive healed wounds [(number positive/n) × 100], and tested for significance (analysis of variance, p < 0.0001; Tukey test, p < 0.05). The data showed that CSS irrigated with nutrient medium were not statistically different in wound area (67.8 ± 5.1%) from murine autografts (63.3 ± 2.9%) but were statistically larger than human xenograft, no graft, or CSS treated with saline irrigation or dry dressings. HLA- ABC expression was 100% in CSS with nutrient irrigation, 86% in CSS with saline irrigation, 83% In CSS without irrigation, and 75% in xenografts with nutrient irrigation. These findings suggest that availability of essential nutrients supports keratinocyte viability during graft vascularization of CSS

Right Isomerism of the Brain in Inversus Viscerum Mutant Mice

Left-right (L-R) asymmetry is a fundamental feature of higher-order neural function. However, the molecular basis of brain asymmetry remains unclear. We recently reported L-R asymmetry of hippocampal circuitry caused by differential allocation of N-methyl-D-aspartate receptor (NMDAR) subunit GluRε2 (NR2B) in hippocampal synapses. Using electrophysiology and immunocytochemistry, here we analyzed the hippocampal circuitry of the inversus viscerum (iv) mouse that has a randomized laterality of internal organs. The iv mouse hippocampus lacks L-R asymmetry, it exhibits right isomerism in the synaptic distribution of the ε2 subunit, irrespective of the laterality of visceral organs. This independent right isomerism of the hippocampus is the first evidence that a distinct mechanism downstream of the iv mutation generates brain asymmetry

legless insertional mutation: morphological, molecular, and genetic characterization.

Limb morphogenesis is an excellent model system to study pattern formation during vertebrate development. The legless (lgl) insertional mutation can serve as a tool to analyze specific events in limb development at the embryologic, genetic, and molecular levels. Hemizygous mice of this transgenic line are phenotypically normal, but homozygous mutants are inviable and exhibit limb, brain, and craniofacial malformations, as well as situs inversus. By morphological analysis of mutant hindlimb buds we show absence of a normal apical ectodermal ridge, a structure required for limb bud outgrowth, and an unusually high degree of mesenchymal and ectodermal cell death. Mutant embryos are extremely sensitive to retinoic acid, a known teratogen with a proposed role in limb development. The hindlimb malformations in legless mutants are less severe when bred into the BALB/c background, suggesting the involvement of other strain-specific genes. Molecular analysis of the disrupted region indicates two tightly linked insertion sites. Sequences flanking the transgene insertions have been cloned and mapped to chromosome 12, near the iv (situs inversus viscerum) locus. Consistent with this, complementation tests confirm allelism of lgl and iv and suggest that the transgene insertion may have disrupted more than one gene. Phylogenetically conserved sequences flanking the transgene insertions were identified and used to isolate candidate lgl and iv cDNAs

The 2017 EULAR standardised procedures for ultrasound imaging in rheumatology

BACKGROUND: In 2001, the European League Against Rheumatism developed and disseminated the first guidelines for musculoskeletal (MS) ultrasound (US) in rheumatology. Fifteen years later, the dramatic expansion of new data on MSUS in the literature coupled with technological developments in US imaging has necessitated an update of these guidelines.OBJECTIVES: To update the existing MSUS guidelines in rheumatology as well as to extend their scope to other anatomic structures relevant for rheumatology.METHODS: The project consisted of the following steps: (1) a systematic literature review of MSUS evaluable structures; (2) a Delphi survey among rheumatologist and radiologist experts in MSUS to select MS and non-MS anatomic structures evaluable by US that are relevant to rheumatology, to select abnormalities evaluable by US and to prioritise these pathologies for rheumatology and (3) a nominal group technique to achieve consensus on the US scanning procedures and to produce an electronic illustrated manual (ie, App of these procedures).RESULTS: Structures from nine MS and non-MS areas (ie, shoulder, elbow, wrist and hand, hip, knee, ankle and foot, peripheral nerves, salivary glands and vessels) were selected for MSUS in rheumatic and musculoskeletal diseases (RMD) and their detailed scanning procedures (ie, patient position, probe placement, scanning method and bony/other landmarks) were used to produce the App. In addition, US evaluable abnormalities present in RMD for each anatomic structure and their relevance for rheumatology were agreed on by the MSUS experts.CONCLUSIONS: This task force has produced a consensus-based comprehensive and practical framework on standardised procedures for MSUS imaging in rheumatology

The geography of biodiversity change in marine and terrestrial assemblages

This work was supported by funding to the sChange working group through sDiv, the synthesis center of iDiv, the German Centre for Integrative Biodiversity Research Halle-Jena-Leipzig, funded by the German Research Foundation (FZT 118). S.A.B., H.B., J.M.C., J.H., and M.W. were supported by the German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig. S.R.S. was supported by U.S. National Science Foundation grant 1400911. LHA was supported by Fundação para a Ciência e Tecnologia, Portugal (POPH/FSE SFRH/BD/90469/2012), and by the Jane and Aatos Erkko Foundation. M.D. was supported by a Leverhulme Trust Fellowship. A.E.M., F.M., and M.D. were supported by ERC AdG BioTIME 250189 and PoC BioCHANGE 727440. A.G. is supported by the Liber Ero Chair in Biodiversity Conservation.Human activities are fundamentally altering biodiversity. Projections of declines at the global scale are contrasted by highly variable trends at local scales, suggesting that biodiversity change may be spatially structured. Here, we examined spatial variation in species richness and composition change using more than 50,000 biodiversity time series from 239 studies and found clear geographic variation in biodiversity change. Rapid compositional change is prevalent, with marine biomes exceeding and terrestrial biomes trailing the overall trend. Assemblage richness is not changing on average, although locations exhibiting increasing and decreasing trends of up to about 20% per year were found in some marine studies. At local scales, widespread compositional reorganization is most often decoupled from richness change, and biodiversity change is strongest and most variable in the oceans.PostprintPostprintPeer reviewe

Mapping human pressures on biodiversity across the planet uncovers anthropogenic threat complexes

Abstract Climate change and other anthropogenic drivers of biodiversity change are unequally distributed across the world. Overlap in the distributions of different drivers have important implications for biodiversity change attribution and the potential for interactive effects. However, the spatial relationships among different drivers and whether they differ between the terrestrial and marine realm has yet to be examined. We compiled global gridded datasets on climate change, land-use, resource exploitation, pollution, alien species potential and human population density. We used multivariate statistics to examine the spatial relationships among the drivers and to characterize the typical combinations of drivers experienced by different regions of the world. We found stronger positive correlations among drivers in the terrestrial than in the marine realm, leading to areas with high intensities of multiple drivers on land. Climate change tended to be negatively correlated with other drivers in the terrestrial realm (e.g. in the tundra and boreal forest with high climate change but low human use and pollution), whereas the opposite was true in the marine realm (e.g. in the Indo-Pacific with high climate change and high fishing). We show that different regions of the world can be defined by Anthropogenic Threat Complexes (ATCs), distinguished by different sets of drivers with varying intensities. We identify 11 ATCs that can be used to test hypotheses about patterns of biodiversity and ecosystem change, especially about the joint effects of multiple drivers. Our global analysis highlights the broad conservation priorities needed to mitigate the impacts of anthropogenic change, with different priorities emerging on land and in the ocean, and in different parts of the world.Peer reviewe

Abnormal resting-state cortical coupling in chronic tinnitus

<p>Abstract</p> <p>Background</p> <p>Subjective tinnitus is characterized by an auditory phantom perception in the absence of any physical sound source. Consequently, in a quiet environment, tinnitus patients differ from control participants because they constantly perceive a sound whereas controls do not. We hypothesized that this difference is expressed by differential activation of distributed cortical networks.</p> <p>Results</p> <p>The analysis was based on a sample of 41 participants: 21 patients with chronic tinnitus and 20 healthy control participants. To investigate the architecture of these networks, we used phase locking analysis in the 1–90 Hz frequency range of a minute of resting-state MEG recording. We found: 1) For tinnitus patients: A significant decrease of inter-areal coupling in the alpha (9–12 Hz) band and an increase of inter-areal coupling in the 48–54 Hz gamma frequency range relative to the control group. 2) For both groups: an inverse relationship (r = -.71) of the alpha and gamma network coupling. 3) A discrimination of 83% between the patient and the control group based on the alpha and gamma networks. 4) An effect of manifestation on the distribution of the gamma network: In patients with a tinnitus history of less than 4 years, the left temporal cortex was predominant in the gamma network whereas in patients with tinnitus duration of more than 4 years, the gamma network was more widely distributed including more frontal and parietal regions.</p> <p>Conclusion</p> <p>In the here presented data set we found strong support for an alteration of long-range coupling in tinnitus. Long-range coupling in the alpha frequency band was decreased for tinnitus patients while long-range gamma coupling was increased. These changes discriminate well between tinnitus and control participants. We propose a tinnitus model that integrates this finding in the current knowledge about tinnitus. Furthermore we discuss the impact of this finding to tinnitus therapies using Transcranial Magnetic Stimulation (TMS).</p

Multidimensional Recording (MDR) and Data Sharing: An Ecological Open Research and Educational Platform for Neuroscience

Primate neurophysiology has revealed various neural mechanisms at the single-cell level and population level. However, because recording techniques have not been updated for several decades, the types of experimental design that can be applied in the emerging field of social neuroscience are limited, in particular those involving interactions within a realistic social environment. To address these limitations and allow more freedom in experimental design to understand dynamic adaptive neural functions, multidimensional recording (MDR) was developed. MDR obtains behavioral, neural, eye position, and other biological data simultaneously by using integrated multiple recording systems. MDR gives a wide degree of freedom in experimental design because the level of behavioral restraint is adjustable depending on the experimental requirements while still maintaining the signal quality. The biggest advantage of MDR is that it can provide a stable neural signal at higher temporal resolution at the network level from multiple subjects for months, which no other method can provide. Conventional event-related analysis of MDR data shows results consistent with previous findings, whereas new methods of analysis can reveal network mechanisms that could not have been investigated previously. MDR data are now shared in the public server Neurotycho.org. These recording and sharing methods support an ecological system that is open to everyone and will be a valuable and powerful research/educational platform for understanding the dynamic mechanisms of neural networks

Low Frequency Vibrations Disrupt Left-Right Patterning in the Xenopus Embryo

The development of consistent left-right (LR) asymmetry across phyla is a fascinating question in biology. While many pharmacological and molecular approaches have been used to explore molecular mechanisms, it has proven difficult to exert precise temporal control over functional perturbations. Here, we took advantage of acoustical vibration to disrupt LR patterning in Xenopus embryos during tightly-circumscribed periods of development. Exposure to several low frequencies induced specific randomization of three internal organs (heterotaxia). Investigating one frequency (7 Hz), we found two discrete periods of sensitivity to vibration; during the first period, vibration affected the same LR pathway as nocodazole, while during the second period, vibration affected the integrity of the epithelial barrier; both are required for normal LR patterning. Our results indicate that low frequency vibrations disrupt two steps in the early LR pathway: the orientation of the LR axis with the other two axes, and the amplification/restriction of downstream LR signals to asymmetric organs

Impacts of past abrupt land change on local biodiversity globally

Abrupt land change, such as deforestation or agricultural intensification, is a key driver of biodiversity change. Following abrupt land change, local biodiversity often continues to be influenced through biotic lag effects. However, current understanding of how terrestrial biodiversity is impacted by past abrupt land changes is incomplete. Here we show that abrupt land change in the past continues to influence present species assemblages globally. We combine geographically and taxonomically broad data on local biodiversity with quantitative estimates of abrupt land change detected within time series of satellite imagery from 1982 to 2015. Species richness and abundance were 4.2% and 2% lower, respectively, and assemblage composition was altered at sites with an abrupt land change compared to unchanged sites, although impacts differed among taxonomic groups. Biodiversity recovered to levels comparable to unchanged sites after >10 years. Ignoring delayed impacts of abrupt land changes likely results in incomplete assessments of biodiversity change