Confocal laser endomicroscopy (pCLE) provides real-time histologic imaging of human tissues at a depth of 60-70 μm during endoscopy. pCLE of the extrahepatic bile duct after fluorescein injection demonstrated a reticular pattern within fluorescein-filled sinuses that had no known anatomical correlate. Freezing biopsy tissue before fixation preserved the anatomy of this structure, demonstrating that it is part of the submucosa and a previously unappreciated fluid-filled interstitial space, draining to lymph nodes and supported by a complex network of thick collagen bundles. These bundles are intermittently lined on one side by fibroblast-like cells that stain with endothelial markers and vimentin, although there is a highly unusual and extensive unlined interface between the matrix proteins of the bundles and the surrounding fluid. We observed similar structures in numerous tissues that are subject to intermittent or rhythmic compression, including the submucosae of the entire gastrointestinal tract and urinary bladder, the dermis, the peri-bronchial and peri-arterial soft tissues, and fascia. These anatomic structures may be important in cancer metastasis, edema, fibrosis, and mechanical functioning of many or all tissues and organs. In sum, we describe the anatomy and histology of a previously unrecognized, though widespread, macroscopic, fluid-filled space within and between tissues, a novel expansion and specification of the concept of the human interstitium.
Biological annihilation via the ongoing sixth mass extinction signaled by vertebrate population losses and declines
- Proceedings of the National Academy of Sciences of the United States of America
- Published about 2 years ago
The population extinction pulse we describe here shows, from a quantitative viewpoint, that Earth’s sixth mass extinction is more severe than perceived when looking exclusively at species extinctions. Therefore, humanity needs to address anthropogenic population extirpation and decimation immediately. That conclusion is based on analyses of the numbers and degrees of range contraction (indicative of population shrinkage and/or population extinctions according to the International Union for Conservation of Nature) using a sample of 27,600 vertebrate species, and on a more detailed analysis documenting the population extinctions between 1900 and 2015 in 177 mammal species. We find that the rate of population loss in terrestrial vertebrates is extremely high-even in “species of low concern.” In our sample, comprising nearly half of known vertebrate species, 32% (8,851/27,600) are decreasing; that is, they have decreased in population size and range. In the 177 mammals for which we have detailed data, all have lost 30% or more of their geographic ranges and more than 40% of the species have experienced severe population declines (>80% range shrinkage). Our data indicate that beyond global species extinctions Earth is experiencing a huge episode of population declines and extirpations, which will have negative cascading consequences on ecosystem functioning and services vital to sustaining civilization. We describe this as a “biological annihilation” to highlight the current magnitude of Earth’s ongoing sixth major extinction event.
The collapse of the Fukushima Dai-ichi Nuclear Power Plant caused a massive release of radioactive materials to the environment. A prompt and reliable system for evaluating the biological impacts of this accident on animals has not been available. Here we show that the accident caused physiological and genetic damage to the pale grass blue Zizeeria maha, a common lycaenid butterfly in Japan. We collected the first-voltine adults in the Fukushima area in May 2011, some of which showed relatively mild abnormalities. The F₁ offspring from the first-voltine females showed more severe abnormalities, which were inherited by the F₂ generation. Adult butterflies collected in September 2011 showed more severe abnormalities than those collected in May. Similar abnormalities were experimentally reproduced in individuals from a non-contaminated area by external and internal low-dose exposures. We conclude that artificial radionuclides from the Fukushima Nuclear Power Plant caused physiological and genetic damage to this species.
Recently we reported the development of prominent exostosis young adults' skulls (41%; 10-31 mm) emanating from the external occipital protuberance (EOP). These findings contrast existing reports that large enthesophytes are not seen in young adults. Here we show that a combination sex, the degree of forward head protraction (FHP) and age predicted the presence of enlarged EOP (EEOP) (n = 1200, age 18-86). While being a male and increased FHP had a positive effect on prominent exostosis, paradoxically, increase in age was linked to a decrease in enthesophyte size. Our latter findings provide a conundrum, as the frequency and severity of degenerative skeletal features in humans are associated typically with aging. Our findings and the literature provide evidence that mechanical load plays a vital role in the development and maintenance of the enthesis (insertion) and draws a direct link between aberrant loading of the enthesis and related pathologies. We hypothesize EEOP may be linked to sustained aberrant postures associated with the emergence and extensive use of hand-held contemporary technologies, such as smartphones and tablets. Our findings raise a concern about the future musculoskeletal health of the young adult population and reinforce the need for prevention intervention through posture improvement education.
Coffee is one of the most consumed beverages world-wide and one of the primary sources of caffeine intake. Given its important health and economic impact, the underlying genetics of its consumption has been widely studied. Despite these efforts, much has still to be uncovered. In particular, the use of non-additive genetic models may uncover new information about the genetic variants driving coffee consumption. We have conducted a genome-wide association study in two Italian populations using additive, recessive and dominant models for analysis. This has uncovered a significant association in the PDSS2 gene under the recessive model that has been replicated in an independent cohort from the Netherlands (ERF). The identified gene has been shown to negatively regulate the expression of the caffeine metabolism genes and can thus be linked to coffee consumption. Further bioinformatics analysis of eQTL and histone marks from Roadmap data has evidenced a possible role of the identified SNPs in regulating PDSS2 gene expression through enhancers present in its intron. Our results highlight a novel gene which regulates coffee consumption by regulating the expression of the genes linked to caffeine metabolism. Further studies will be needed to clarify the biological mechanism which links PDSS2 and coffee consumption.
The energy requirement of species at each trophic level in an ecological pyramid is a function of the number of organisms and their average mass. Regarding human populations, although considerable attention is given to estimating the number of people, much less is given to estimating average mass, despite evidence that average body mass is increasing. We estimate global human biomass, its distribution by region and the proportion of biomass due to overweight and obesity.
The gecko genus Geckolepis, endemic to Madagascar and the Comoro archipelago, is taxonomically challenging. One reason is its members ability to autotomize a large portion of their scales when grasped or touched, most likely to escape predation. Based on an integrative taxonomic approach including external morphology, morphometrics, genetics, pholidosis, and osteology, we here describe the first new species from this genus in 75 years: Geckolepis megalepissp. nov. from the limestone karst of Ankarana in northern Madagascar. The new species has the largest known body scales of any gecko (both relatively and absolutely), which come off with exceptional ease. We provide a detailed description of the skeleton of the genus Geckolepis based on micro-Computed Tomography (micro-CT) analysis of the new species, the holotype of G. maculata, the recently resurrected G. humbloti, and a specimen belonging to an operational taxonomic unit (OTU) recently suggested to represent G. maculata. Geckolepis is characterized by highly mineralized, imbricated scales, paired frontals, and unfused subolfactory processes of the frontals, among other features. We identify diagnostic characters in the osteology of these geckos that help define our new species and show that the OTU assigned to G. maculata is probably not conspecific with it, leaving the taxonomic identity of this species unclear. We discuss possible reasons for the extremely enlarged scales of G. megalepis in the context of an anti-predator defence mechanism, and the future of Geckolepis taxonomy.
Obtaining high-quality samples from wild animals is a major obstacle for genomic studies of many taxa, particularly at the population level, as collection methods for such samples are typically invasive. DNA from feces is easy to obtain noninvasively, but is dominated by bacterial and other non-host DNA. The high proportion of non-host DNA drastically reduces the efficiency of high-throughput sequencing for host animal genomics. To address this issue, we developed an inexpensive capture method for enriching host DNA from noninvasive fecal samples. Our method exploits natural differences in CpG-methylation density between vertebrate and bacterial genomes to preferentially bind and isolate host DNA from majority-bacterial samples. We demonstrate that the enrichment is robust, efficient, and compatible with downstream library preparation methods useful for population studies (e.g., RADseq). Compared to other enrichment strategies, our method is quick and inexpensive, adding only a negligible cost to sample preparation. In combination with downstream methods such as RADseq, our approach allows for cost-effective and customizable genomic-scale genotyping that was previously feasible in practice only with invasive samples. Because feces are widely available and convenient to collect, our method empowers researchers to explore genomic-scale population-level questions in organisms for which invasive sampling is challenging or undesirable.
- Proceedings of the National Academy of Sciences of the United States of America
- Published about 4 years ago
Antiaging therapies show promise in model organism research. Translation to humans is needed to address the challenges of an aging global population. Interventions to slow human aging will need to be applied to still-young individuals. However, most human aging research examines older adults, many with chronic disease. As a result, little is known about aging in young humans. We studied aging in 954 young humans, the Dunedin Study birth cohort, tracking multiple biomarkers across three time points spanning their third and fourth decades of life. We developed and validated two methods by which aging can be measured in young adults, one cross-sectional and one longitudinal. Our longitudinal measure allows quantification of the pace of coordinated physiological deterioration across multiple organ systems (e.g., pulmonary, periodontal, cardiovascular, renal, hepatic, and immune function). We applied these methods to assess biological aging in young humans who had not yet developed age-related diseases. Young individuals of the same chronological age varied in their “biological aging” (declining integrity of multiple organ systems). Already, before midlife, individuals who were aging more rapidly were less physically able, showed cognitive decline and brain aging, self-reported worse health, and looked older. Measured biological aging in young adults can be used to identify causes of aging and evaluate rejuvenation therapies.
The CRISPR-associated endonuclease Cas9 binds to a guide RNA and cleaves double-stranded DNA with a sequence complementary to the RNA guide. The Cas9-RNA system has been harnessed for numerous applications, such as genome editing. Here we use high-speed atomic force microscopy (HS-AFM) to visualize the real-space and real-time dynamics of CRISPR-Cas9 in action. HS-AFM movies indicate that, whereas apo-Cas9 adopts unexpected flexible conformations, Cas9-RNA forms a stable bilobed structure and interrogates target sites on the DNA by three-dimensional diffusion. These movies also provide real-time visualization of the Cas9-mediated DNA cleavage process. Notably, the Cas9 HNH nuclease domain fluctuates upon DNA binding, and subsequently adopts an active conformation, where the HNH active site is docked at the cleavage site in the target DNA. Collectively, our HS-AFM data extend our understanding of the action mechanism of CRISPR-Cas9.