Plant invasion into an 'Ohi'a tree fern rain forest following experimental canopy opening

Western Region, National Park Servic

Posterior segment eye disease in sub-Saharan Africa: review of recent population-based studies.

OBJECTIVE: To assess the burden of posterior segment eye diseases (PSEDs) in sub-Saharan Africa (SSA). METHODS: We reviewed published population-based data from SSA and other relevant populations on the leading PSED, specifically glaucoma, diabetic retinopathy and age-related macular degeneration, as causes of blindness and visual impairment in adults. Data were extracted from population-based studies conducted in SSA and elsewhere where relevant. RESULTS: PSEDs, when grouped or as individual diseases, are a major contributor to blindness and visual impairment in SSA. PSED, grouped together, was usually the second leading cause of blindness after cataract, ranging as a proportion of blindness from 13 to 37%. CONCLUSIONS: PSEDs are likely to grow in importance as causes of visual impairment and blindness in SSA in the coming years as populations grow, age and become more urban in lifestyle. African-based cohort studies are required to help estimate present and future needs and plan services to prevent avoidable blindness

Increased Epithelial Expression of CTGF and S100A7 with Elevated Subepithelial Expression of IL-1β in Trachomatous Trichiasis.

PURPOSE: To characterize the histological appearance and expression of pro-inflammatory mediators, growth factors, matrix metalloproteinases and biomarkers of epithelial-mesenchymal transition (EMT) in healthy control and trachomatous trichiasis (TT) conjunctival tissue. METHODS: Conjunctival biopsies were taken from 20 individuals with TT and from 16 individuals with healthy conjunctiva, which served as controls. Study participants were of varying ethnicity and were living in a trachoma-endemic region of northern Tanzania. Formalin-fixed paraffin-embedded tissue sections were stained using hematoxylin and eosin or by immunohistochemistry using antibodies against: IL-1β, IL-6, IL-17A, IL-22, CXCL5, S100A7, cleaved caspase 1 (CC1), PDGF, CTGF, TGFβ2, MMP7, MMP9, E-cadherin, vimentin, and αSMA. RESULTS: Tissue from TT cases had a greater inflammatory cell infiltrate relative to controls and greater disruption of collagen structure. CTGF and S100A7 were more highly expressed in the epithelium and IL-1β was more highly expressed in the substantia propria of TT cases relative to controls. Latent TGFβ2 was slightly more abundant in the substantia propria of control tissue. No differences were detected between TT cases and controls in the degree of epithelial atrophy, the number of myofibroblasts or expression of EMT biomarkers. CONCLUSIONS: These data indicate that the innate immune system is active in the immunopathology of trachoma, even in the absence of clinical inflammation. CTGF might provide a direct link between inflammation and fibrosis and could be a suitable target for therapeutic treatment to halt the progression of trachomatous scarring

Cervical, Thoracic, and Spinopelvic Compensation After Proximal Junctional Kyphosis (PJK): Does Location of PJK Matter?

Study Design:Retrospective case series. Objective:Compensatory changes above a proximal junctional kyphosis (PJK) have not been defined. Understanding these mechanisms may help determine optimal level selection when performing revision for PJK. This study investigates how varying PJK location changes proximal spinal alignment. Methods:Patients were grouped by upper instrumented vertebrae (UIV): lower thoracic (LT; T8-L1) or upper thoracic (UT; T1-7). Alignment parameters were compared. Correlation analysis was performed between PJK magnitude and global/cervical alignment. Results:A total of 369 patients were included; mean age of 63 years, body mass index 28, and 81% female, LT (n = 193) versus UT (n = 176). The rate of radiographic PJK was 49%, higher in the LT group (55% vs 42%, P = .01). The UT group displayed significant differences in all cervical radiographic parameters (P < .05) between PJK versus non-PJK patients, while the LT group displayed significant differences in T1S and C2-T3 sagittal vertical axis (SVA) (CTS). In comparing UT versus LT patients, UT had more posterior global alignment (smaller TPA [T1 pelvic angle], SVA, and larger PT [pelvic tilt]) and larger anterior cervical alignment (greater cSVA [cervical SVA], T1S-CL [T1 slope-cervical lordosis] mismatch, CTS) compared to LT. Correlation analysis of PJK magnitude and location demonstrated a correlation with increases in CL, T1S, and CTS in the UT group. In the LT group, PT increased with PJK angle (r = 0.17) and no significant correlations were noted to SVA, cSVA, or T1S-CL. Conclusions:PJK location influences compensation mechanisms of the cervical and thoracic spine. LT PJK results in increased PT and CL with decreased CTS. UT PJK increases CL to counter increases in T1S with continued T1S-CL mismatch and elevated cSVA

A mechanochemical model of striae distensae

Striae distensae, otherwise known as stretch marks, are common skin lesions found in a variety of clinical settings. They occur frequently during adolescence or pregnancy where there is rapid tissue expansion and in clinical situations associated with corticosteroid excess. Heralding their onset is the appearance of parallel inflammatory streaks aligned perpendicular to the direction of skin tension. Despite a considerable amount of investigative research, the pathogenesis of striae remains obscure. The interpretation of histologic samples – the major investigative tool – demonstrates an association between dermal lymphocytic inflammation, elastolysis, and a scarring response. Yet the primary causal factor in their aetiology is mechanical; either skin stretching due to underlying tissue expansion or, less frequently, a compromised dermis affected by normal loads. In this paper, we investigate the pathogenesis of striae by addressing the coupling between mechanical forces and dermal pathology. We develop a mathematical model that incorporates the mechanical properties of cutaneous fibroblasts and dermal extracellular matrix. By using linear stability analysis and numerical simulations of our governing nonlinear equations, we show that this quantitative approach may provide a realistic framework that may account for the initiating events

Assessing hydrological controls on the lithium isotope weathering tracer

To investigate the impact of riverine discharge and weathering intensity on lithium isotopes (δ7Li) in a mono-lithological terrain, this study examines the dissolved load and leached suspended load (exchangeable, oxide, and clay fractions) from Icelandic rivers spanning a wide range of discharge, weathering rates, and weathering intensity. The δ7Lidissolved co-varies inversely with the discharge, confirming that water-rock interaction time is a primary control on the secondary mineral formation that fractionates Li isotopes. The “boomerang” shape observed in global rivers between the weathering intensity (i.e. W/D = weathering rate/denudation rate) and δ7Lidissolved also exists for these basaltic rivers at low to medium W/D. However, these rivers do not extend to such low δ7Lidissolved values as seen in the global compilation at low W/D, indicating that there is a lithological control on this relationship arising from the type of the lithology-specific secondary minerals forming and their precipitation rates. In addition, the Δ7Lix-dissolved between each leached solid phase and the dissolved load also co-varies with discharge. At low discharge (long water-rock interaction times), Δ7Lix-dissolved values agree with experimentally-determined equilibrium values, whereas less fractionated values are observed at higher discharge (shorter water-rock interaction times). As a result, there is a different relationship between W/D and Δ7Liclay-source in this basaltic terrain than previously reported from global multi-lithological river sediment samples, with clay leachates from Iceland more closely mimicking the boomerang shape of the dissolved load. However, the relationship between δ7Li and weathering processes is complicated because the fractionation between the clay fraction and the dissolved load is not constant but varies with both W/D and discharge. Overall, this study confirms the utility of Li isotopes as a tracer of modern and palaeo-weathering processes, and also has important implications for the specific interpretations of detrital δ7Li values, which may be more sensitive to weathering parameters than previously thought

Assessing hydrological controls on the lithium isotope weathering tracer

To investigate the impact of riverine discharge and weathering intensity on lithium isotopes (δ7Li) in a mono-lithological terrain, this study examines the dissolved load and leached suspended load (exchangeable, oxide, and clay fractions) from Icelandic rivers spanning a wide range of discharge, weathering rates, and weathering intensity. The δ7Lidissolved co-varies inversely with the discharge, confirming that water-rock interaction time is a primary control on the secondary mineral formation that fractionates Li isotopes. The “boomerang” shape observed in global rivers between the weathering intensity (i.e. W/D = weathering rate/denudation rate) and δ7Lidissolved also exists for these basaltic rivers at low to medium W/D. However, these rivers do not extend to such low δ7Lidissolved values as seen in the global compilation at low W/D, indicating that there is a lithological control on this relationship arising from the type of the lithology-specific secondary minerals forming and their precipitation rates. In addition, the Δ7Lix-dissolved between each leached solid phase and the dissolved load also co-varies with discharge. At low discharge (long water-rock interaction times), Δ7Lix-dissolved values agree with experimentally-determined equilibrium values, whereas less fractionated values are observed at higher discharge (shorter water-rock interaction times). As a result, there is a different relationship between W/D and Δ7Liclay-source in this basaltic terrain than previously reported from global multi-lithological river sediment samples, with clay leachates from Iceland more closely mimicking the boomerang shape of the dissolved load. However, the relationship between δ7Li and weathering processes is complicated because the fractionation between the clay fraction and the dissolved load is not constant but varies with both W/D and discharge. Overall, this study confirms the utility of Li isotopes as a tracer of modern and palaeo-weathering processes, and also has important implications for the specific interpretations of detrital δ7Li values, which may be more sensitive to weathering parameters than previously thought

Immunohistochemical Analysis of Scarring Trachoma Indicates Infiltration by Natural Killer and Undefined CD45 Negative Cells.

INTRODUCTION: The phenotype and function of immune cells infiltrating the conjunctiva in scarring trachoma have yet to be fully characterized. We assessed tissue morphology and immunophenotype of cellular infiltrates found in trachomatous scarring compared to control participants. METHODOLOGY: Clinical assessments and conjunctival biopsy samples were obtained from 34 individuals with trachomatous scarring undergoing trichiasis surgery and 33 control subjects undergoing cataract or retinal detachment surgery. Biopsy samples were fixed in buffered formalin and embedded in paraffin wax. Hematoxylin and eosin (H&E) staining was performed for assessment of the inflammatory cell infiltrate. Immunohistochemical staining of single markers on individual sections was performed to identify cells expressing CD3 (T-cells), CD4 (helper T-cells), CD8 (suppressor/cytotoxic T-cells and Natural Killer, NK, cells), NCR1 (NK cells), CD20 (B-cells), CD45 (nucleated hematopoietic cells), CD56 (NK and T-cells), CD68 (macrophages/monocytes) and CD83 (mature dendritic cells). The degree of scarring was assessed histologically using cross-polarized light to visualize collagen fibres. PRINCIPLE FINDINGS: Scarring, regardless of clinical inflammation, was associated with increased inflammatory cell infiltrates on H&E and CD45 staining. Scarring was also associated with increased CD8+ and CD56+ cells, but not CD3+ cells, suggestive of a NK cell infiltrate. This was supported by the presence of NCR1+ cells. There was some increase in CD20+ cells, but no evidence for increased CD4+, CD68+ or CD83+ cells. Numerous CD45 negative cells were also seen in the population of infiltrating inflammatory cells in scarred conjunctiva. Disorganization of the normal collagen architecture was strongly associated with clinical scarring. CONCLUSIONS/SIGNIFICANCE: These data point to the infiltration of immune cells with a phenotype suggestive of NK cells in conjunctival trachomatous scarring. A large proportion of CD45 negative inflammatory cells were also present. Future work should seek to understand the stimuli leading to the recruitment of these cells and their role in progressive scarring

Application of the LymphGen classification tool to 928 clinically and genetically-characterised cases of diffuse large B cell lymphoma (DLBCL).

We recently published results of targeted sequencing applied to 928 unselected cases of DLBCL registered in the Haematological Malignancy Research Network (HMRN) registry (1). Clustering allowed us to resolve five genomic subtypes. These subtypes shared considerable overlap with those proposed in two independent genomic studies(2, 3), suggesting the potential to use genetics to stratify patients by both risk and biology. In the original studies, clustering techniques were applied to sample cohorts to reveal molecular substructure, but left open the challenge of how to classify an individual patient. This was addressed by the LymphGen classification tool (4). LymphGen assigns an individual case to one of six molecular subtypes. The tool accommodates data from exome or targeted sequencing, either with or without copy number variant (CNV) data. Separate gene expression data allows classification of a seventh, MYC-driven subtype defined by a double hit (DHL) or molecular high-grade (MHG) gene expression signature(5-7).HR was funded by a studentship from the Medical Research Council. DH was supported by a Clinician Scientist Fellowship from the Medical Research Council (MR/M008584/1). The Hodson laboratory receives core funding from Wellcome and MRC to the Wellcome-MRC Cambridge Stem Cell Institute and core funding from the CRUK Cambridge Cancer Centre. HMRN is supported by BCUK 15037 and CRUK 18362

Deletion of the Imprinted Phlda2 Gene Increases Placental Passive Permeability in the Mouse

Genomic imprinting, an epigenetic phenomenon that causes the expression of a small set of genes in a parent-of-origin-specific manner, is thought to have co-evolved with placentation. Many imprinted genes are expressed in the placenta, where they play diverse roles related to development and nutrient supply function. However, only a small number of imprinted genes have been functionally tested for a role in nutrient transfer capacity in relation to the structural characteristics of the exchange labyrinthine zone. Here, we examine the transfer capacity in a mouse model deficient for the maternally expressed Phlda2 gene, which results in placental overgrowth and a transient reduction in fetal growth. Using stereology, we show that the morphology of the labyrinthine zone in Phlda2−/+ mutants is normal at E16 and E19. In vivo placental transfer of radiolabeled solutes 14C-methyl-D-glucose and 14C-MeAIB remains unaffected at both gestational time points. However, placental passive permeability, as measured using two inert hydrophilic solutes (14C-mannitol; 14C-inulin), is significantly higher in mutants. Importantly, this increase in passive permeability is associated with fetal catch-up growth. Our findings uncover a key role played by the imprinted Phlda2 gene in modifying placental passive permeability that may be important for determining fetal growth