The phylogeography and population genetic structure of least cisco (Coregonus sardinella) in Alaska

Thesis (M.S.) University of Alaska Fairbanks, 2013The least cisco (Coregonus sardinella) is a whitefish species broadly distributed across the Arctic regions of Russia, Alaska, and Canada, and little is known about the genetic relationships among groups within this species. We investigated the genetic relationships among least cisco on two landscape scales. On a broader landscape scale, we investigated the relationships among populations across the state of Alaska by comparing mitochondria) DNA (mtDNA) sequences. On a finer landscape scale, we investigated the relationships among least cisco populations in closely located lakes on the Arctic Coastal Plain by comparing microsatellite DNA haplotypes. Data from mtDNA suggest that least cisco are relatively diverse across Alaska, with 68 unique haplotypes found in 305 individuals and a large proportion of genetic variation is shared across Alaska, but this variation is not homogeneously distributed across all regions and for all haplotype groups. Interpretation of microsatellite data was limited. Overall, the data suggest that least cisco populations are currently isolated from one another. Isolation also occurred historically, accounting for divergence among major Glades. But general recontact events occurred as isolated populations migrated and colonized new habitats, accounting for the heterogeneity found across Alaska. Ultimately, Alaskan least cisco may have functioned as a metapopulation historically, but present populations are too isolated to be considered a metapopulation today

Marine debris in the Bering Sea: combining historical records, toxicology, and local knowledge to assess impacts and identify solutions

Dissertation (Ph.D.) University of Alaska Fairbanks, 2022Marine debris, particularly plastic marine debris, has numerous impacts on the environment, wildlife, and human communities. This research examines dimensions of marine debris in the Bering Sea and Aleutian Islands, Alaska, including impacts of marine debris pollution on wildlife and the environment; the history of marine debris research, monitoring, and cleanup activities; and community perspectives on local to global solutions. The first chapter of this dissertation is an integrative literature review to better understand the current status of marine debris knowledge in the Bering Sea region and identify critical knowledge gaps. We synthesized the depth and breadth of research, monitoring, and cleanup activities to better understand the sources, prevalence, and impacts of marine debris on wildlife and coastal communities. Our review revealed several knowledge gaps, including two that were a focus of the final chapters of the dissertation: measuring the extent of plastic-associated contaminants in the Bering Sea and capturing community perspectives and concerns about marine debris in the Bering Sea. The second chapter examined variation in phthalates, a class of plastic-associated chemicals, in Aleutian Islands seabirds, to refine hypotheses regarding ecological and environmental factors that affect phthalate exposure in marine wildlife. We quantified phthalates in seabirds collected across >1700 km of the Aleutian Islands, Alaska, and measured six phthalate congeners in seabirds representing ten species and four feeding guilds. Phthalates were detected in 100% of specimens (n = 115) but varied among individuals (range 3.64 - 539.64 ng/g). Total phthalates did not vary geographically, but differed among feeding guilds, with significantly higher concentrations in diving plankton-feeders compared to others. Our findings suggest feeding behavior could influence exposure risk for seabirds and lend further evidence to the ubiquity of plastic pollutants in marine ecosystems. The final chapter of the dissertation explored perspectives and concerns of St. Paul Island community members regarding marine debris and plastic pollution. This component of the research aimed to catalyze the inclusion of local knowledge in marine debris solutions for St. Paul Island, Alaska, by documenting community members' perceptions of marine debris, including its origin, impacts, and proposed solutions. We interviewed thirty-six St. Paul Island community members from 2017 to 2020 about the types, amount, distribution, and impacts of marine debris they have observed on the island and its surrounding waters over recent decades. Research participants reported increases in plastic debris since the 1980s, particularly plastic bottles. Nearly 80% expressed concern about impacts to subsistence resources, including entanglement and ingestion of plastic particles by marine mammals and fishes. St. Paul Island community members' experiences highlight that solving the problem of marine debris cannot rely on local efforts alone but requires broader policies and mitigation strategies to address the sources of debris and advance environmental justice for coastal communities. Overall, this dissertation contributes an improved understanding of the social and ecological impacts of plastic pollution in the Bering Sea region and the potential science and policy solutions that can stem the tide of marine debris.Conoco PhillipsChapter 1: General introduction -- Chapter 2: A review of marine debris impacts and multi-scale solutions to plastic pollution in Bering Sea social-ecological systems -- Chapter 3: Plastic-derived contaminants in Aleutian Archipelago seabirds with varied foraging strategies -- Chapter 4: Including coastal community voices in the marine debris conversation: Perspectives from St. Paul Island, Alaska -- Chapter 5: General conclusion -- Appendices

Elongation factor Tu is a multifunctional and processed moonlighting protein

Many bacterial moonlighting proteins were originally described in medically, agriculturally, and commercially important members of the low G + C Firmicutes. We show Elongation factor Tu (Ef-Tu) moonlights on the surface of the human pathogens Staphylococcus aureus (SaEf-Tu) and Mycoplasma pneumoniae (MpnEf-Tu), and the porcine pathogen Mycoplasma hyopneumoniae (MhpEf-Tu). Ef-Tu is also a target of multiple processing events on the cell surface and these were characterised using an N-terminomics pipeline. Recombinant MpnEf-Tu bound strongly to a diverse range of host molecules, and when bound to plasminogen, was able to convert plasminogen to plasmin in the presence of plasminogen activators. Fragments of Ef-Tu retain binding capabilities to host proteins. Bioinformatics and structural modelling studies indicate that the accumulation of positively charged amino acids in short linear motifs (SLiMs), and protein processing promote multifunctional behaviour. Codon bias engendered by an A + T rich genome may influence how positively-charged residues accumulate in SLiMs

Ganglioside-induced differentiation associated protein 1 is a regulator of the mitochondrial network: new implications for Charcot-Marie-Tooth disease

Mutations in GDAP1 lead to severe forms of the peripheral motor and sensory neuropathy, Charcot-Marie-Tooth disease (CMT), which is characterized by heterogeneous phenotypes, including pronounced axonal damage and demyelination. We show that neurons and Schwann cells express ganglioside-induced differentiation associated protein 1 (GDAP1), which suggest that both cell types may contribute to the mixed features of the disease. GDAP1 is located in the mitochondrial outer membrane and regulates the mitochondrial network. Overexpression of GDAP1 induces fragmentation of mitochondria without inducing apoptosis, affecting overall mitochondrial activity, or interfering with mitochondrial fusion. The mitochondrial fusion proteins, mitofusin 1 and 2 and Drp1(K38A), can counterbalance the GDAP1-dependent fission. GDAP1-specific knockdown by RNA interference results in a tubular mitochondrial morphology. GDAP1 truncations that are found in patients who have CMT are not targeted to mitochondria and have lost mitochondrial fragmentation activity. The latter activity also is reduced strongly for disease-associated GDAP1 point mutations. Our data indicate that an exquisitely tight control of mitochondrial dynamics, regulated by GDAP1, is crucial for the proper function of myelinated peripheral nerves

A leverage points perspective on Arctic Indigenous food systems research: A systematic review

Arctic food systems are increasingly challenged by rapid climate change, loss of food security and subsequent weakening of food sovereignty, and destabilization of Indigenous practices. Despite growing scientific knowledge on Arctic food systems, Indigenous communities continue to struggle with a plethora of sustainability challenges. To develop a systemic understanding of these challenges, we performed a systematic review of 526 articles published between 1998 and 2021 on Arctic Indigenous food systems. We used the leverage points framework to structure our analysis to understand to what extent the existing Western scientific body of literature provides the necessary knowledge to understand the food system characteristics that give rise to the current sustainability challenges. We combined deductive qualitative and inductive quantitative approaches to identify gaps in the systemic understanding of Arctic Indigenous food systems. We characterized existing research across the four levels of systemic depth—parameters, feedbacks, design, intent—and identified promising directions for future research. Our analyses show that research on food systems is clustered within six main domains, we term environmental contaminants, diet and health, food security, food culture and economy, changing socio-ecological systems and marine and coast. Based on our analysis, we identify three directions for future research that we believe to be of particular importance to enable sustainability transformations of Arctic Indigenous food systems: (i) the decolonization of research practices, (ii) acknowledging the significance of systemic interdependencies across shallow and deep leverage points, and (iii) transdisciplinary action-oriented research collaborations directing transformative system interventions

Molecular, cellular and physiological characterization of the cancer cachexia-inducing C26 colon carcinoma in mouse

BACKGROUND: The majority of cancer patients experience dramatic weight loss, due to cachexia and consisting of skeletal muscle and fat tissue wasting. Cachexia is a negative prognostic factor, interferes with therapy and worsens the patients' quality of life by affecting muscle function. Mice bearing ectopically-implanted C26 colon carcinoma are widely used as an experimental model of cancer cachexia. As part of the search for novel clinical and basic research applications for this experimental model, we characterized novel cellular and molecular features of C26-bearing mice. METHODS: A fragment of C26 tumor was subcutaneously grafted in isogenic BALB/c mice. The mass growth and proliferation rate of the tumor were analyzed. Histological and cytofluorometric analyses were used to assess cell death, ploidy and differentiation of the tumor cells. The main features of skeletal muscle atrophy, which were highlighted by immunohistochemical and electron microscopy analyses, correlated with biochemical alterations. Muscle force and resistance to fatigue were measured and analyzed as major functional deficits of the cachectic musculature. RESULTS: We found that the C26 tumor, ectopically implanted in mice, is an undifferentiated carcinoma, which should be referred to as such and not as adenocarcinoma, a common misconception. The C26 tumor displays aneuploidy and histological features typical of transformed cells, incorporates BrdU and induces severe weight loss in the host, which is largely caused by muscle wasting. The latter appears to be due to proteasome-mediated protein degradation, which disrupts the sarcomeric structure and muscle fiber-extracellular matrix interactions. A pivotal functional deficit of cachectic muscle consists in increased fatigability, while the reported loss of tetanic force is not statistically significant following normalization for decreased muscle fiber size. CONCLUSIONS: We conclude, on the basis of the definition of cachexia, that ectopically-implanted C26 carcinoma represents a well standardized experimental model for research on cancer cachexia. We wish to point out that scientists using the C26 model to study cancer and those using the same model to study cachexia may be unaware of each other's works because they use different keywords; we present strategies to eliminate this gap and discuss the benefits of such an exchange of knowledge

Management of pregnancy in autoimmune rheumatic diseases: maternal disease course, gestational and neonatal outcomes and use of medications in the prospectiveItalian P-RHEUM.it study

Objectives To investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it. Methods Pregnant women with different ARD were enrolled for up to 20 gestational weeks in 29 Rheumatology Centres for 5 years (2018-2023). Maternal and infant information were collected in a web-based database. Results We analysed 866 pregnancies in 851 patients (systemic lupus erythematosus was the most represented disease, 19.6%). Maternal disease flares were observed in 135 (15.6%) pregnancies. 53 (6.1%) pregnancies were induced by assisted reproduction techniques, 61 (7%) ended in miscarriage and 11 (1.3%) underwent elective termination. Obstetrical complications occurred in 261 (30.1%) pregnancies, including 2.3% pre-eclampsia. Two cases of congenital heart block were observed out of 157 pregnancies (1.3%) with anti-Ro/SSA. Regarding treatments, 244 (28.2%) pregnancies were treated with glucocorticoids, 388 (44.8%) with hydroxychloroquine, 85 (9.8%) with conventional synthetic disease-modifying anti-rheumatic drugs and 122 (14.1%) with biological disease-modifying anti-rheumatic drugs. Live births were 794 (91.7%), mostly at term (84.9%); four perinatal deaths (0.5%) occurred. Among 790 newborns, 31 (3.9%) were small-for-gestational-age and 169 (21.4%) had perinatal complications. Exclusive maternal breast feeding was received by 404 (46.7%) neonates. The Edinburgh Postnatal Depression Scale was compiled by 414 women (52.4%); 89 (21.5%) scored positive for emotional distress. Conclusions Multiple factors including preconception counselling and treat-to-target with pregnancy-compatible medications may have contributed to mitigate disease-related risk factors, yielding limited disease flares, good pregnancy outcomes and frequency of complications which were similar to the Italian general obstetric population. Disease-specific issues need to be further addressed to plan preventative measures

The combination of limb-bud removal and in ovo electroporation techniques: A new powerful method to study gene function in motoneurons undergoing lesion-induced cell death

AbstractBackgroundThe chicken embryo is an important model organism for developmental biology studies. At present, many techniques on this model have been set up, from surgical procedures to molecular biology methods, to answer capital questions of cell biology. The study of the genes involved in motoneurons (MNs) survival and cell death is critical for a better understanding of the molecular mechanisms leading to MNs degenerative diseases, such as amyothophic lateral sclerosis (ALS) and motor peripheral neuropathies.New methodHere, we describe the combination of a well known surgical procedure able to induce MNs cell death, the limb-bud removal (LBR), with a very popular method used in molecular biology to test gene function in living organisms, the in ovo electroporation (IOE). The aim of this work is to provide an effective method for the investigation of genes involved in MNs survival and cell death under lesion conditions.ResultsOur method allows the successful electroporation of the 40–50% of MNs on the side of LBR with a high survival rate early and late after procedure.Comparison with other methodsThis modified LBR technique combined with IOE allows a higher MN expression efficiency compared to an already published method.ConclusionsOur work opens the possibility of screening a multitude of genes involved in MNs survival or cell death in vivo with high reproducibility and efficiency on a flexible and inexpensive animal model. The LBR/IOE technique opens a new way for the optimization of subsequent studies on mammalian models of diseases affecting MNs survival