Biology subjects

Sampson, L.

Publications and source records attributed to Sampson, L..

2 recordsLinked to original sources

bioRxiv2023

The MODY-associated TALK-1 L114P mutation causes islet α-cell overactivity and β-cell inactivity resulting in transient neonatal diabetes and glucose dyshomeostasis in adults

The gain-of-function mutation in the TALK-1 K+ channel (p.L114P) is associated with maturity-onset diabetes of the young (MODY). TALK-1 is a key regulator of {beta}-cell electrical activity and glucose-stimulated insulin secretion. The KCNK16 gene encoding TALK-1 is the most abundant and {beta}-cell-restricted K+ channel transcript. To investigate the impact of KCNK16 L114P on glucose homeostasis and confirm its association with MODY, a mouse model containing the Kcnk16 L114P mutation was generated. Heterozygous and homozygous Kcnk16 L114P mice exhibit increased neonatal lethality in the C57BL/6J and the CD-1(ICR) genetic background, respectively. Lethality is likely a result of severe hyperglycemia observed in the homozygous Kcnk16 L114P neonates due to lack of glucose-stimulated insulin secretion and can be reduced with insulin treatment. Kcnk16 L114P increased whole-cell {beta}-cell K+ currents resulting in blunted glucose-stimulated Ca2+ entry and loss of glucose-induced Ca2+ oscillations. Thus, adult Kcnk16 L114P mice have reduced glucose-stimulated insulin secretion and plasma insulin levels, which significantly impairs glucose homeostasis. Taken together, this study shows that the MODY-associated Kcnk16 L114P mutation disrupts glucose homeostasis in adult mice resembling a MODY phenotype and causes neonatal lethality by inhibiting islet insulin secretion during development. These data suggest that TALK-1 is an islet-restricted target for the treatment for diabetes. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC="FIGDIR/small/545631v3_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@19031e9org.highwire.dtl.DTLVardef@1bccc49org.highwire.dtl.DTLVardef@803e1org.highwire.dtl.DTLVardef@36c584_HPS_FORMAT_FIGEXP M_FIG Graphical Summary C_FIG

physiology↗

bioRxiv2020

The rise of disease ecology

Micro- and macroparasites are a leading cause of mortality for humans, animals, and plants, and there is great need to understand their origins, transmission dynamics, and impacts. Disease ecology formed as an interdisciplinary field in the 1970s to fill this need and has recently rapidly grown in size and influence. Because interdisciplinary fields integrate diverse scientific expertise and training experiences, understanding their composition and research priorities is often difficult. Here, for the first time, we quantify the composition and educational experiences of a subset of disease ecology practitioners and identify topical trends in published research. We combined a large survey of self-declared disease ecologists with a literature synthesis involving machine-learning topic detection of over 18,500 disease ecology research articles. The number of graduate degrees earned by disease ecology practitioners has grown dramatically since the early 2000s. Similar to other science fields, we show that practitioners in disease ecology have diversified in the last decade in terms of gender identity and institution, with weaker diversification in race and ethnicity. Topic detection analysis revealed how the frequency of publications on certain topics have declined (e.g., HIV, serology), increased (e.g., the dilution effect, infectious disease in bats), remained relatively common (e.g., malaria ecology, influenza, vaccine research and development), or have consistently remained relatively infrequent (e.g., theoretical models, field experiments). Other topics, such as climate change, superspreading, emerging infectious diseases, and network analyses, have recently come to prominence. This study helps identify the major themes of disease ecology and demonstrates how publication frequency corresponds to emergent health and environmental threats. More broadly, our approach provides a framework to examine the composition and publication trends of other major research fields that cross traditional disciplinary boundaries.

ecology↗