Tyrosine-fed rats develop corneal disease which mimics that found in the human metabolic disorder, tyrosinosis. By electron and polarizing microscopy needle-shaped birefringent crystals are ...demonstrable in early corneal epithelial lesions of tyronsine-fed rats. The crystals appear as negative images by electron microscopy, their content apparently extracted by fixation and/or embedding fluids. Crystals may be arranged in sheaves or bundles and pass from one cell to another disrupting the continuity of membranes of both cells and nuclei. They are present in desquamating epithelial cells along corneal ulcers. Polarizing microscopy of whole mounts of diseased tissue shows that the crystals are limited to epithelial lesion areas. We hypothesize that the crystals are tyrosine and that crystal growth in cells initiates lesion and subsequent ulcer formation.
Many major corporations and countries have made commitments to purchase or produce only “sustainable” palm oil, a commodity responsible for substantial tropical forest loss. Sustainability ...certification is the tool most used to fulfill these procurement policies, and around 20% of global palm oil production was certified by the Roundtable on Sustainable Palm Oil (RSPO) in 2017. However, the effect of certification on deforestation in oil palm plantations remains unclear. Here, we use a comprehensive dataset of RSPO-certified and noncertified oil palm plantations (∼188,000 km²) in Indonesia, the leading producer of palm oil, as well as annual remotely sensed metrics of tree cover loss and fire occurrence, to evaluate the impact of certification on deforestation and fire from 2001 to 2015. While forest loss and fire continued after RSPO certification, certified palm oil was associated with reduced deforestation. Certification lowered deforestation by 33% from a counterfactual of 9.8 to 6.6% y−1. Nevertheless, most plantations contained little residual forest when they received certification. As a result, by 2015, certified areas held less than 1% of forests remaining within Indonesian oil palm plantations. Moreover, certification had no causal impact on forest loss in peatlands or active fire detection rates. Broader adoption of certification in forested regions, strict requirements to avoid all peat, and routine monitoring of clearly defined forest cover loss in certified and RSPO member-held plantations appear necessary if the RSPO is to yield conservation and climate benefits from reductions in tropical deforestation.
Mucus, with its burden of inspired particulates and pathogens, is cleared from mucosal surfaces of the airways by cilia beating within the periciliary layer (PCL). The PCL is held to be "watery" and ...free of mucus by thixotropic-like forces arising from beating cilia. With radii of gyration ~250 nm, however, polymeric mucins should reptate readily into the PCL, so we assessed the glycocalyx for barrier functions. The PCL stained negative for MUC5AC and MUC5B, but it was positive for keratan sulfate (KS), a glycosaminoglycan commonly associated with glycoconjugates. Shotgun proteomics showed KS-rich fractions from mucus containing abundant tethered mucins, MUC1, MUC4, and MUC16, but no proteoglycans. Immuno-histology by light and electron microscopy localized MUC1 to microvilli, MUC4 and MUC20 to cilia, and MUC16 to goblet cells. Electron and atomic force microscopy revealed molecular lengths of 190-1,500 nm for tethered mucins, and a finely textured glycocalyx matrix filling interciliary spaces. Adenoviral particles were excluded from glycocalyx of the microvilli, whereas the smaller adenoassociated virus penetrated, but were trapped within. Hence, tethered mucins organized as a space-filling glycocalyx function as a selective barrier for the PCL, broadening their role in innate lung defense and offering new molecular targets for conventional and gene therapies.
The simplest and arguably the most ubiquitous pattern in seed dispersal mutualisms is size coupling: large frugivores tend to consume larger fruits and small frugivores tend to consume smaller ...fruits. Despite the simplicity of this pattern, the potential mechanisms responsible for fruit–frugivore size coupling are mechanistically divergent and poorly resolved. Size coupling could arise deterministically, if large frugivores actively seek out larger fruits to maximize their foraging efficiency. Alternatively, size coupling could also arise passively, if frugivores forage randomly, but are able to consume only those fruit species that are smaller than their gape width. I observed birds forage for fruits in a New Zealand forest reserve at approximately five‐day intervals for six years to test for fruit–frugivore size coupling. I then derived a suite of network analyses to establish whether fruit–frugivore size coupling was best explained by active or passive foraging by frugivores. Results showed a strikingly strong pattern in size coupling; the average size of fruits consumed by each frugivore species increased with their maximum gape width. Simulation analyses revealed that over 70% of variation in interaction frequencies in the observed fruit–frugivore web could be explained by a size‐constrained, passive, foraging model. Foraging models in which birds foraged actively for different‐sized fruits to improve their foraging efficiency performed more poorly. Results were therefore consistent with the hypothesis that apparently nonrandom patterns in seed dispersal mutualisms can sometimes arise from simple stochastic processes.
The paradox of island evolution Burns, K. C.
Journal of biogeography,
February 2022, 2022-02-00, 20220201, Letnik:
49, Številka:
2
Journal Article
Recenzirano
Aim
After colonising isolated islands, many types of plants and animals undergo extreme morphological diversification. In stark contrast, other island taxa change more subtly and converge ...evolutionarily on intermediate body size (the island rule). This paradox of island evolution has gone undetected for decades, perhaps because each pattern has been investigated separately using different analytical tools. Here, I investigate the paradox of island evolution in the endemic floras of four oceanic archipelagos in the Southwest Pacific.
Location
Chatham, Kermadec, Lord Howe & Norfolk Islands.
Taxon
Woody plants.
Methods
I test whether the sizes of ‘solitary endemics’ (species that evolved anagenetically in the absence of co‐occurring endemic congeners) are correlated with their closest mainland ancestors. I also test whether island–mainland size relationships in 'solitary endemics' differ from isometry, as predicted by the island rule. Next, I test whether the stature of ‘co‐occurring endemics’ (closely related, often cladogenetic species) exhibits exaggerated differentiation.
Results
The stature of 'solitary endemics' was correlated with their mainland relatives, and two out of the four archipelagos showed evidence of the island rule. On the other hand, the stature of 'co‐occurring endemics' was unrelated to their closest mainland relatives and often highly differentiated.
Main conclusions
Overall results suggest that the island paradox arises from two distinct evolutionary pathways. Solitary endemics evolve more slowly and often converge on intermediate morphology, while co‐occurring endemics evolve more rapidly and often exhibit highly differentiated morphology. Future work aimed at a better understanding of the mechanisms underpinning the island paradox could help to further unite phylogenetic work on adaptive radiations and macroecological tests of the island rule under a single conceptual umbrella.
Glioblastoma multiforme is the most common primary malignant brain tumour, with a median survival of about one year. This poor prognosis is due to therapeutic resistance and tumour recurrence after ...surgical removal. Precisely how recurrence occurs is unknown. Using a genetically engineered mouse model of glioma, here we identify a subset of endogenous tumour cells that are the source of new tumour cells after the drug temozolomide (TMZ) is administered to transiently arrest tumour growth. A nestin-ΔTK-IRES-GFP (Nes-ΔTK-GFP) transgene that labels quiescent subventricular zone adult neural stem cells also labels a subset of endogenous glioma tumour cells. On arrest of tumour cell proliferation with TMZ, pulse-chase experiments demonstrate a tumour re-growth cell hierarchy originating with the Nes-ΔTK-GFP transgene subpopulation. Ablation of the GFP+ cells with chronic ganciclovir administration significantly arrested tumour growth, and combined TMZ and ganciclovir treatment impeded tumour development. Thus, a relatively quiescent subset of endogenous glioma cells, with properties similar to those proposed for cancer stem cells, is responsible for sustaining long-term tumour growth through the production of transient populations of highly proliferative cells.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
With the introduction of spectral-domain optical coherence tomography (OCT), much larger image datasets are routinely acquired compared to what was possible using the previous generation of ...time-domain OCT. Thus, the need for 3-D segmentation methods for processing such data is becoming increasingly important. We report a graph-theoretic segmentation method for the simultaneous segmentation of multiple 3-D surfaces that is guaranteed to be optimal with respect to the cost function and that is directly applicable to the segmentation of 3-D spectral OCT image data. We present two extensions to the general layered graph segmentation method: the ability to incorporate varying feasibility constraints and the ability to incorporate true regional information. Appropriate feasibility constraints and cost functions were learned from a training set of 13 spectral-domain OCT images from 13 subjects. After training, our approach was tested on a test set of 28 images from 14 subjects. An overall mean unsigned border positioning error of 5.69 plusmn 2.41 mum was achieved when segmenting seven surfaces (six layers) and using the average of the manual tracings of two ophthalmologists as the reference standard. This result is very comparable to the measured interobserver variability of 5.71 plusmn 1.98 mum.
Total knee arthroplasty (TKA) is a common and costly surgical procedure. Despite high success rates, many TKA patients develop chronic pain in the months and years following surgery, constituting a ...public health burden. Pain catastrophizing is a construct that reflects anxious preoccupation with pain, inability to inhibit pain-related fears, amplification of the significance of pain vis-à-vis health implications, and a sense of helplessness regarding pain. Recent research suggests that it may be an important risk factor for untoward TKA outcomes. To clarify this impact, we systematically reviewed the literature to date on pain catastrophizing as a prospective predictor of chronic pain following TKA.
We searched MEDLINE, EMBASE, and PsycINFO databases to identify articles related to pain catastrophizing, TKA, risk models, and chronic pain. We reviewed titles and abstracts to identify original research articles that met our specified inclusion criteria. Included articles were then rated for methodological quality. including methodological quality. Due to heterogeneity in follow-up, analyses, and outcomes reported across studies, a quantitative meta-analysis could not be performed.
We identified six prospective longitudinal studies with small-to-mid-sized samples that met the inclusion criteria. Despite considerable variability in reported pain outcomes, pain catastrophizing was identified as a significant predictor of chronic pain persisting ≥3 months following TKA in five of the studies assessed. Limitations of studies included lack of large-scale data, absence of standardized pain measurements, inadequate multivariate adjustment, such as failure to control for analgesic use and other relevant covariates, and failure to report non-significant parameter estimates.
This study provides moderate-level evidence for pain catastrophizing as an independent predictor of chronic pain post-TKA. Directions for future research include larger, well-controlled studies with standard pain outcomes, identification of clinically-relevant catastrophizing cut-offs that predict pain outcomes, investigation of other psychosocial risk factors, and assessment of interventions aimed to reduce pain catastrophizing on chronic pain outcomes following TKA surgery.
A central question in glioblastoma multiforme (GBM) research is the identity of the tumor-initiating cell, and its contribution to the malignant phenotype and genomic state. We examine the potential ...of adult lineage-restricted progenitors to induce fully penetrant GBM using CNS progenitor-specific inducible Cre mice to mutate Nf1, Trp53, and Pten. We identify two phenotypically and molecularly distinct GBM subtypes governed by identical driver mutations. We demonstrate that the two subtypes arise from functionally independent pools of adult CNS progenitors. Despite histologic identity as GBM, these tumor types are separable based on the lineage of the tumor-initiating cell. These studies point to the cell of origin as a major determinant of GBM subtype diversity.
•Adult lineage-restricted CNS progenitors, like stem cells, can give rise to GBM•Two different GBM-initiating CNS progenitors are induced by identical mutations•Histologically and molecularly distinct GBMs arise from different CNS progenitors•The cell of origin emerges as a major determinant of GBM molecular subtype
Alcantara Llaguno et al. examine the potential of adult CNS lineage-restricted progenitors to induce fully penetrant glioblastoma multiforme (GBM) and show that the same genetic drivers in different cells of origin generate molecularly distinct GBM subtypes.
Bone is a dynamically remodeled tissue that requires gravity-mediated mechanical stimulation for maintenance of mineral content and structure. Homeostasis in bone occurs through a balance in the ...activities and signaling of osteoclasts, osteoblasts, and osteocytes, as well as proliferation and differentiation of their stem cell progenitors. Microgravity and unloading are known to cause osteoclast-mediated bone resorption; however, we hypothesize that osteocytic osteolysis, and cell cycle arrest during osteogenesis may also contribute to bone loss in space. To test this possibility, we exposed 16-week-old female C57BL/6J mice (n = 8) to microgravity for 15-days on the STS-131 space shuttle mission. Analysis of the pelvis by µCT shows decreases in bone volume fraction (BV/TV) of 6.29%, and bone thickness of 11.91%. TRAP-positive osteoclast-covered trabecular bone surfaces also increased in microgravity by 170% (p = 0.004), indicating osteoclastic bone degeneration. High-resolution X-ray nanoCT studies revealed signs of lacunar osteolysis, including increases in cross-sectional area (+17%, p = 0.022), perimeter (+14%, p = 0.008), and canalicular diameter (+6%, p = 0.037). Expression of matrix metalloproteinases (MMP) 1, 3, and 10 in bone, as measured by RT-qPCR, was also up-regulated in microgravity (+12.94, +2.98 and +16.85 fold respectively, p<0.01), with MMP10 localized to osteocytes, and consistent with induction of osteocytic osteolysis. Furthermore, expression of CDKN1a/p21 in bone increased 3.31 fold (p<0.01), and was localized to osteoblasts, possibly inhibiting the cell cycle during tissue regeneration as well as conferring apoptosis resistance to these cells. Finally the apoptosis inducer Trp53 was down-regulated by -1.54 fold (p<0.01), possibly associated with the quiescent survival-promoting function of CDKN1a/p21. In conclusion, our findings identify the pelvic and femoral region of the mouse skeleton as an active site of rapid bone loss in microgravity, and indicate that this loss is not limited to osteoclastic degradation. Therefore, this study offers new evidence for microgravity-induced osteocytic osteolysis, and CDKN1a/p21-mediated osteogenic cell cycle arrest.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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