Tracing dust in the Southern Hemisphere over the last glacial cycle

Mineral dust both influences and is influenced by climate on many timescales, from seconds to epochs. Its complex interactions with the climate system are still being unraveled. For example, dust fluxes change in tandem with other records of past changes in climate, and dust source is often presumed to change as well, in response to shifts in climate conditions in source regions; changes in wind regimes; or changes in atmospheric transport pathways. In this work, I investigate dust records from the Southern Hemisphere from ice core and marine sediment core climate archives, looking at both flux and provenance in order elucidate the conditions that allowed for those particles to travel from source to sink. Using multiple radiogenic isotope systems as tracers (87Sr/86Sr, εNd(0), 206Pb/207Pb, and 208Pb/207Pb), I geochemically “fingerprint” of dust particles from Southern Hemisphere climate archives over the last glacial cycle. I compare the dust fingerprints to potential source areas (PSA’s) from across the Southern Hemisphere in order to identify the sources of dust found in the WAIS Divide and Taylor Glacier ice cores from West Antarctica, as well as from marine sediment core ELT39.75 in the Tasman Sea. I use endmember mixing theory to determine the relative contribution of different sources to the climate archives over time. In West Antarctica, I geochemically identify specific local volcanoes from Marie Byrd Land as significant particle contributors to the WAIS Divide ice core during the previous glacial period. In the Tasman Sea, I identify a specific region of southeastern Australia as primary the dust source over the past glacial cycle, with the source remaining constant across glacial-interglacial climate transitions. This clarifies that the “fingerprint” of Australian dust is relatively invariant over time and allows a single Australian signature to be used as an endmember for identifying dust provenance in climate archives downwind. I also identify the dust sources in the WAIS Divide during the Last Glacial Maximum and through the early deglacial, identifying southern South America as the predominant source during cold stages. WAIS Divide and Taylor Glacier dust records do not record dust source changes across millennial-scale climate events, suggesting that a) the source regions did not change, b) the transport pathways remained pinned, or c) the proxy is not sensitive to changes in these variables. Contributions from local volcanoes are also inferred from the WAIS dust record using mixing theory. In summary, I find that the radiogenic isotope fingerprint of dust samples from the archives analyzed show subtle or no changes in source over climate transitions, and therefore the strategy of dust particles as a tracer of past atmospheric circulation pathways should be approached cautiously

Cholemic Nephropathy: Hyperbilirubinemia and its Impact on Renal Function

Cholemic nephropathy represents a spectrum of renal injury, from proximal tubulopathy to intrarenal bile cast formation, found in patients with severe liver dysfunction. It is caused by hyperbilirubinemia, usually in jaundiced patients. Acute kidney injury is one of the most important complications in patients with end-stage liver disease. The relationship between liver disease and renal impairment, especially the effect of hyperbilirubinemia on renal tissue and renal function, has not been fully elucidated. These considerations deem necessary for nephrologists, when performing a clinical evaluation of patients with liver diseases, for the implementation of an integrated medical approach. This review focuses on the current knowledge on cholemic nephropathy with emphasis on the role of hyperbilirubinemia on renal impairment. The treatment strategies and outcome are also discussed

Evaluation of Safety of a Newly Formulated Pirfenidone in Chronic Kidney Disease: A Non-Randomized Pilot Study in Mexican Patients

The aim of this pilot clinical trial was to evaluate the safety of a new formulation of prolonged-release Pirfenidone (PR-PFD) in chronic kidney disease (CKD), specifically focal and segmental glomerular hyalinization (FSGH). Open-label, pilot, nonrandomized trial. Eighteen patients previously diagnosed with CKD stages 1– 5 according to “Kidney Disease: Improving Global Outcomes” were enrolled in the study. Target dos-age of PFD was 1200 mg twice a day in the form of prolonged-release tablets to reach a full dosage of 2400 mg daily. Clinical trial was carried out for 60 months to evaluate the safety and efficacy of a newly formulated PR-PFD in patients with CKD. After the treatment for 60 months, it was found that PR-PFD kept renal function from declining significantly in CKD patients, as the glomerular filtration rate (GFR) showed only minimal variations throughout the study. Estimated glomerular filtration rate (eGFR) showed no differences at both baseline and the end points. Proteinuria improved, and creatinine, cystatin C, urea, hemoglobin and hepatic transaminases remained constant without any considerable changes across the study. Minor side effects were noticed when compared with those found in previous studies, indicating an increased tolerance to this pharmaceutical formulation of PFD. Prolonged-released PFD could be safely used as an adjuvant therapy in patients with CKD.Registry number was obtained from ClinicalTrials.gov (NCT02408744)

East Greenland ice core dust record reveals timing of Greenland ice sheet advance and retreat.

Accurate estimates of the past extent of the Greenland ice sheet provide critical constraints for ice sheet models used to determine Greenland's response to climate forcing and contribution to global sea level. Here we use a continuous ice core dust record from the Renland ice cap on the east coast of Greenland to constrain the timing of changes to the ice sheet margin and relative sea level over the last glacial cycle. During the Holocene and the previous interglacial period (Eemian) the dust record was dominated by coarse particles consistent with rock samples from central East Greenland. From the coarse particle concentration record we infer the East Greenland ice sheet margin advanced from 113.4 +/- 0.4 to 111.0 +/- 0.4 ka BP during the glacial onset and retreated from 12.1 +/- 0.1 to 9.0 +/- 0.1 ka BP during the last deglaciation. These findings constrain the possible response of the Greenland ice sheet to climate forcings

Liver fibrosis secondary to bile duct injury: correlation of Smad7 with TGF-β and extracellular matrix proteins

<p>Abstract</p> <p>Background</p> <p>Liver fibrosis is the result of continuous liver injury stemming from different etiological factors. Bile duct injury induces an altered expression of TGF-β, which has an important role in liver fibrosis because this cytokine induces the expression of target genes such as collagens, PAI-1, TIMPs, and others that lead to extracellular matrix deposition. Smad7 is the principal inhibitor that regulates the target gene transcription of the TGF-β signaling. The aim of the study was to determine whether Smad7 mRNA expression correlates with the gene expression of <it>TGF-β, Col I</it>, <it>Col III</it>, <it>Col IV</it>, or <it>PAI-1 </it>in liver fibrosis secondary to bile duct injury (BDI).</p> <p>Results</p> <p>Serum TGF-β concentration was higher in BDI patients (39 296 pg/ml) than in liver donors (9008 pg/ml). Morphometric analysis of liver sections showed 41.85% of tissue contained fibrotic deposits in BDI patients. mRNA expression of Smad7, Col I, and PAI-1 was also significantly higher (<it>P </it>< 0.05) in patients with BDI than in controls. Smad7 mRNA expression correlated significantly with TGF-β concentration, Col I and Col III expression, and the amount of fibrosis.</p> <p>Conclusion</p> <p>We found augmented serum concentration of TGF-β and an increase in the percentage of fibrotic tissue in the liver of BDI patients. Contrary to expected results, the 6-fold increase in <it>Smad7 </it>expression did not inhibit the expression of <it>TGF-β, collagens</it>, and <it>PAI-1</it>. We also observed greater expression of Col I and Col III mRNA in BDI patients and significant correlations between their expression and TGF-β concentration and Smad7 mRNA expression.</p

"If we can do it, anyone can": Paper Chase Collaborative Writing Exercise for Engaging Students in Research Dissemination

Involving students in research is a high-impact educational practice, and students often lack opportunities for involvement in successful collaborative research dissemination. Undergraduate and graduate students can benefit&nbsp; by engaging in manuscript development for writing skills and research dissemination for career trajectory benefits, similar to the importance of faculty communicating their science. Despite the many motivations to publish research findings, persistent barriers exist and delay time to publication. Faculty, especially women and Black, Indigenous, and People of Color, face challenges in publishing research (e.g. lower rates of funding, higher service demands). The Paper Chase model is an intensive process of structured writing for collaborative manuscript development. This approach provides opportunities for students to engage in the dissemination phase through manuscript development and publication. Though often done with lab or research teams of known authors, we created a competitive program to connect students previously unfamiliar with the project to work with a faculty's Paper Chase team. Our professional development program involved basic training on writing, academic publishing, and effective group communication with a culminating event of team-based writing. We will present data from our two campus-wide Paper Chase events, held virtually and in-person. We conducted pre- and post-surveys of participants: faculty (n=10), undergraduate (n=40) and graduate students (n=14). Results demonstrate feasibility, acceptability, and positive outcomes associated with the Paper Chase program. We also present challenges and lessons learned. Conducting Paper Chase events on campus can boost faculty members' productivity, students' understanding of research dissemination, and improve confidence in writing practices for all

PPARs as Metabolic Sensors and Therapeutic Targets in Liver Diseases

Carbohydrates and lipids are two components of the diet that provide the necessary energy to carry out various physiological processes to help maintain homeostasis in the body. However, when the metabolism of both biomolecules is altered, development of various liver diseases takes place; such as metabolic-associated fatty liver diseases (MAFLD), hepatitis B and C virus infections, alcoholic liver disease (ALD), and in more severe cases, hepatocelular carcinoma (HCC). On the other hand, PPARs are a family of ligand-dependent transcription factors with an important role in the regulation of metabolic processes to hepatic level as well as in other organs. After interaction with specific ligands, PPARs are translocated to the nucleus, undergoing structural changes to regulate gene transcription involved in lipid metabolism, adipogenesis, inflammation and metabolic homeostasis. This review aims to provide updated data about PPARs’ critical role in liver metabolic regulation, and their involvement triggering the genesis of several liver diseases. Information is provided about their molecular characteristics, cell signal pathways, and the main pharmacological therapies that modulate their function, currently engaged in the clinic scenario, or in pharmacological development