The impacts of voluntary private lands programs on stream fish diversity in the Kaskaskia River Basin, Illinois

Freshwaters support over 40% of fish species diversity, as well as one-third of all vertebrate species, yet remain one of the most threatened habitats globally. Anthropogenic disturbances have caused many negative impacts throughout history, and continue to do so today. After the dust bowl we began to inch our way toward smarter management of our watersheds. This eventually spurred the development of best management practices (BMPs) to combat non-point source pollution. Voluntary private lands programs such as the Conservation Reserve Program (CRP) look to offer monetary incentives to landowners willing to implement conservation practices on their lands. Biological goals, such as increased native bird or fish populations, are sometimes included in programs like CRP but little has been done to evaluate whether those goals are being achieved or not. Sampling can often be expensive for these endeavors, so alternative measures for obtaining this information are valuable. Species distribution modeling (SDM) has provided us with a chance to gain more information about communities without additional sampling effort. I look to balance sampling efforts with species distribution modeling to investigate the effects of CRP of stream fish species richness. In this study, I use data from two Illinois fisheries datasets in combination with GIS environmental data to predict the presence or absence of 64 fish species across the Kaskaskia River basin using random forest classification. Of the 64 modeled species, 52 SDMs met my model performance requirements (TSS>0.2). These 52 SDMs were then stacked to obtain an index of species richness across the basin, and then the species richness values were compared with observed richness of modeled species, via regression, for accuracy. The regression deviated from the ideal 1:1 line, but Theil’s Inequality Coefficient indicated a very strong matchup between observed and predicted richness (U=0.012). Based on this, I concluded that my SDMs were able to provide a reasonable representation of species richness when the predictions of individual species models were stacked. I then developed a novel standardization method using a house-neighborhood framework. “Neighborhoods”, all stream reaches within a given waterway distance from a site, were built around a group of fish sampling sites in the Kaskaskia River basin, Illinois. The species richness of the neighborhood was then used to standardize species richness at fish sampling sites. It is expected that a site in a neighborhood with high species richness would have more species than a site in a neighborhood with low species richness. Standardization based on the neighborhood species richness removes this species pool effect. Logit regression was then used to assess the effect of local habitat variables including CRP on species richness. Proportion of CRP lands within the local watershed for sampled sites ranged from 0% to 45.13%. Using the dredge function within the MuMIn package in R, all possible models were explored. R2 values were low across all models, ranging from R2 = 0.0915 to R2 = 0.2367. The best models (ΔAIC<2) took various combinations of in-stream habitat characteristics with large substrate consistently being ranked as one of the most important variables for species richness. The proportion of CRP lands in the local watershed was not taken as a predictor for any of the top models, while local habitat variables were found to be the most common factors influencing species richness. In conclusion, my study was unable to detect any major influence from CRP on stream fish species richness, and shows that local habitat factors are drivers of species richness when removing species pool effects from models. More rigorous targeting in the CRP implementation plans may help to increase the effect that CRP lands can have on fish species richness

Surgical Excision of Heterotopic Ossification Leads to Re‐Emergence of Mesenchymal Stem Cell Populations Responsible for Recurrence

Trauma‐induced heterotopic ossification (HO) occurs after severe musculoskeletal injuries and burns, and presents a significant barrier to patient rehabilitation. Interestingly, the incidence of HO significantly increases with repeated operations and after resection of previous HO. Treatment of established heterotopic ossification is challenging because surgical excision is often incomplete, with evidence of persistent heterotopic bone. As a result, patients may continue to report the signs or symptoms of HO, including chronic pain, nonhealing wounds, and joint restriction. In this study, we designed a model of recurrent HO that occurs after surgical excision of mature HO in a mouse model of hind‐limb Achilles’ tendon transection with dorsal burn injury. We first demonstrated that key signaling mediators of HO, including bone morphogenetic protein signaling, are diminished in mature bone. However, upon surgical excision, we have noted upregulation of downstream mediators of osteogenic differentiation, including pSMAD 1/5. Additionally, surgical excision resulted in re‐emergence of a mesenchymal cell population marked by expression of platelet‐derived growth factor receptor‐α (PDGFRα) and present in the initial developing HO lesion but absent in mature HO. In the recurrent lesion, these PDGFRα+ mesenchymal cells are also highly proliferative, similar to the initial developing HO lesion. These findings indicate that surgical excision of HO results in recurrence through similar mesenchymal cell populations and signaling mechanisms that are present in the initial developing HO lesion. These results are consistent with findings in patients that new foci of ectopic bone can develop in excision sites and are likely related to de novo formation rather than extension of unresected bone. Stem Cells Translational Medicine 2017;6:799–806Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136492/1/sct312067.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136492/2/sct312067-sup-0001-suppinfo1.pd

Diminished Chondrogenesis and Enhanced Osteoclastogenesis in Leptin-Deficient Diabetic Mice (ob/ob) Impair Pathologic, Trauma-Induced Heterotopic Ossification

Diabetic trauma patients exhibit delayed postsurgical wound, bony healing, and dysregulated bone development. However, the impact of diabetes on the pathologic development of ectopic bone or heterotopic ossification (HO) following trauma is unknown. In this study, we use leptin-deficient mice as a model for type 2 diabetes to understand how post-traumatic HO development may be affected by this disease process. Male leptin-deficient (ob/ob) or wild-type (C57BL/6 background) mice aged 6?8 weeks underwent 30% total body surface area burn injury with left hind limb Achilles tenotomy. Micro-CT (?CT) imaging showed significantly lower HO volumes in diabetic mice compared with wild-type controls (0.70 vs. 7.02?mm3, P?Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140207/1/scd.2015.0135.pd

DNA topoisomerases participate in fragility of the oncogene RET

Fragile site breakage was previously shown to result in rearrangement of the RET oncogene, resembling the rearrangements found in thyroid cancer. Common fragile sites are specific regions of the genome with a high susceptibility to DNA breakage under conditions that partially inhibit DNA replication, and often coincide with genes deleted, amplified, or rearranged in cancer. While a substantial amount of work has been performed investigating DNA repair and cell cycle checkpoint proteins vital for maintaining stability at fragile sites, little is known about the initial events leading to DNA breakage at these sites. The purpose of this study was to investigate these initial events through the detection of aphidicolin (APH)-induced DNA breakage within the RET oncogene, in which 144 APHinduced DNA breakpoints were mapped on the nucleotide level in human thyroid cells within intron 11 of RET, the breakpoint cluster region found in patients. These breakpoints were located at or near DNA topoisomerase I and/or II predicted cleavage sites, as well as at DNA secondary structural features recognized and preferentially cleaved by DNA topoisomerases I and II. Co-treatment of thyroid cells with APH and the topoisomerase catalytic inhibitors, betulinic acid and merbarone, significantly decreased APH-induced fragile site breakage within RET intron 11 and within the common fragile site FRA3B. These data demonstrate that DNA topoisomerases I and II are involved in initiating APH-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication

Coordinating Tissue Regeneration Through Transforming Growth Factorâ β Activated Kinase 1 Inactivation and Reactivation

Aberrant wound healing presents as inappropriate or insufficient tissue formation. Using a model of musculoskeletal injury, we demonstrate that loss of transforming growth factorâ β activated kinase 1 (TAK1) signaling reduces inappropriate tissue formation (heterotopic ossification) through reduced cellular differentiation. Upon identifying increased proliferation with loss of TAK1 signaling, we considered a regenerative approach to address insufficient tissue production through coordinated inactivation of TAK1 to promote cellular proliferation, followed by reactivation to elicit differentiation and extracellular matrix production. Although the current regenerative medicine paradigm is centered on the effects of drug treatment (â drug onâ ), the impact of drug withdrawal (â drug offâ ) implicit in these regimens is unknown. Because current TAK1 inhibitors are unable to phenocopy genetic Tak1 loss, we introduce the dualâ inducible COmbinational Sequential Inversion ENgineering (COSIEN) mouse model. The COSIEN mouse model, which allows us to study the response to targeted drug treatment (â drug onâ ) and subsequent withdrawal (â drug offâ ) through genetic modification, was used here to inactivate and reactivate Tak1 with the purpose of augmenting tissue regeneration in a calvarial defect model. Our study reveals the importance of both the â drug onâ (Creâ mediated inactivation) and â drug offâ (Flpâ mediated reactivation) states during regenerative therapy using a mouse model with broad utility to study targeted therapies for disease. Stem Cells 2019;37:766â 778Manipulating transforming growth factor βâ activated kinase 1 for cell and scaffold free tissue regeneration using a dualâ inducible Combinational Sequential Inversion Engineering mouse model.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149573/1/stem2991_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149573/2/stem2991.pd

Purging Deleterious Mutations under Self Fertilization: Paradoxical Recovery in Fitness with Increasing Mutation Rate in Caenorhabditis elegans

Background: The accumulation of deleterious mutations can drastically reduce population mean fitness. Self-fertilization is thought to be an effective means of purging deleterious mutations. However, widespread linkage disequilibrium generated and maintained by self-fertilization is predicted to reduce the efficacy of purging when mutations are present at multiple loci. Methodology/Principal Findings: We tested the ability of self-fertilizing populations to purge deleterious mutations at multiple loci by exposing obligately self-fertilizing populations of Caenorhabditis elegans to a range of elevated mutation rates and found that mutations accumulated, as evidenced by a reduction in mean fitness, in each population. Therefore, purging in obligate selfing populations is overwhelmed by an increase in mutation rate. Surprisingly, we also found that obligate and predominantly self-fertilizing populations exposed to very high mutation rates exhibited consistently greater fitness than those subject to lesser increases in mutation rate, which contradicts the assumption that increases in mutation rate are negatively correlated with fitness. The high levels of genetic linkage inherent in self-fertilization could drive this fitness increase. Conclusions: Compensatory mutations can be more frequent under high mutation rates and may alleviate a portion of the fitness lost due to the accumulation of deleterious mutations through epistatic interactions with deleterious mutations. Th

Naturally Occurring Lipid A Mutants in Neisseria meningitidis from Patients with Invasive Meningococcal Disease Are Associated with Reduced Coagulopathy

Neisseria meningitidis is a major cause of bacterial meningitis and sepsis worldwide. Lipopolysaccharide (LPS), a major component of the Gram-negative bacterial outer membrane, is sensed by mammalian cells through Toll-like receptor 4 (TLR4), resulting in activation of proinflammatory cytokine pathways. TLR4 recognizes the lipid A moiety of the LPS molecule, and the chemical composition of the lipid A determines how well it is recognized by TLR4. N. meningitidis has been reported to produce lipid A with six acyl chains, the optimal number for TLR4 recognition. Indeed, meningococcal sepsis is generally seen as the prototypical endotoxin-mediated disease. In the present study, we screened meningococcal disease isolates from 464 patients for their ability to induce cytokine production in vitro. We found that around 9% of them were dramatically less potent than wild-type strains. Analysis of the lipid A of several of the low-activity strains by mass spectrometry revealed they were penta-acylated, suggesting a mutation in the lpxL1 or lpxL2 genes required for addition of secondary acyl chains. Sequencing of these genes showed that all the low activity strains had mutations that inactivated the lpxL1 gene. In order to see whether lpxL1 mutants might give a different clinical picture, we investigated the clinical correlate of these mutations in a prospective nationwide observational cohort study of adults with meningococcal meningitis. Patients infected with an lpxL1 mutant presented significantly less frequently with rash and had higher thrombocyte counts, consistent with reduced cytokine induction and less activation of tissue-factor mediated coagulopathy. In conclusion, here we report for the first time that a surprisingly large fraction of meningococcal clinical isolates have LPS with underacylated lipid A due to mutations in the lpxL1 gene. The resulting low-activity LPS may have an important role in virulence by aiding the bacteria to evade the innate immune system. Our results provide the first example of a specific mutation in N. meningitidis that can be correlated with the clinical course of meningococcal disease