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Biology subjects

Lopez, K. A.

Publications and source records attributed to Lopez, K. A..

3 recordsLinked to original sources

Recent divergence and microgeographic genetic structure in an endangered Australian songbird: the southern black-throated finch

Anthropogenic habitat loss and climate change threaten global biodiversity. Effective conservation management requires a detailed understanding of geographic structure, genetic diversity, and demography of threatened species. The black-throated finch, Poephila cincta, is an Australian songbird with two subspecies: atropygialis and cincta. The southern subspecies, cincta, has experienced an [~]80% range contraction over the last century and is listed as endangered but genetic surveys of it are incomplete. Here, we use a combination of reduced representation and whole genome sequencing to examine genetic differentiation, spatial genetic structure, and demographic history in both forms of this species. We find that atropygialis and cincta are genetically distinct despite a history of divergence with gene flow and geographically isolated by a biogeographic barrier known as the Einasleigh Uplands. Since they last shared a common ancestor [~]400,000 years ago, the two subspecies have experienced distinct demographic trajectories: population expansion in atropygialis and population decline in cincta. We find that the two remnant population centers of cincta, from the Galilee Basin and the Townsville Coastal Plain, each represent genetically distinct lineages that last shared appreciable levels of gene flow [~]4,000 years ago. Moreover, we report striking microgeographic genetic structure from the Townsville Coastal Plain between populations <20 km apart associated with barriers to dispersal caused by anthropogenic habitat modification over the last 50 years: namely the construction of the Ross River Dam. Our findings highlight the urgent need for a conservation approach that prioritizes habitat restoration to re-establish population connectivity in the endangered southern black-throated finch.

evolutionary biology↗

Effects of short-term isolation on vocal and non-vocal social behaviors in prairie voles

Social isolation affects the brain and behavior in a variety of animals, including humans. Studies in traditional laboratory rodents, including mice and rats, have supported the idea that short-term social isolation promotes affiliative social behaviors, while long-term isolation promotes anti-social behaviors, including increased aggression. Whether the effects of isolation on the social behaviors of mice and rats generalize to other rodents remains understudied. In the current study, we characterized the effects of short-term (3-days) social isolation on the vocal and non-vocal social behaviors of adult prairie voles (Microtus ochrogaster) during same-sex and opposite-sex social interactions. Our experiments revealed that short-term isolation did not affect rates of ultrasonic vocalizations or time spent in non-aggressive social behaviors and huddling. In contrast, short-term isolation affected aggression in a sex- and context-specific manner during male-male interactions. Our findings highlight the importance of comparative work across species and the consideration of social context to understand the diverse ways in which social isolation can impact social behavior.

animal behavior and cognition↗

Therapeutic targeting of SETD2-deficient cancer cells with the small-molecule compound RITA

The histone methyltransferase SETD2 and its associated histone mark H3 lysine 36 trimethylation (H3K36me3) are frequently lost in certain cancer types, identifying SETD2 as an important therapeutic target. Here we show that SETD2-deficient cancer cells are profoundly sensitive to the compound RITA, resulting in significant p53 induction and apoptosis. This is further associated with defects in DNA replication, leading to delays in S-phase progression, increased recruitment of replication stress markers, and reduced replication fork progression. RITA sensitivity is linked to the phenol sulphotransferase SULT1A1, which we find to be highly upregulated in cells that lack SETD2. Depletion of SULT1A1 or addition of the phenol sulphotransferase inhibitor DCNP abolishes these phenotypes and suppresses the sensitivity of SETD2-deficient cancer cells, identifying SULT1A1 activity to be critical in mediating the potent cytotoxicity of RITA against SETD2-deficient cells. These findings define a novel therapeutic strategy for targeting the loss of SETD2 in cancer. Significance StatementThe histone-modifying enzyme SETD2 has emerged as an important tumour suppressor in a number of different cancer types, identifying it as a promising therapeutic target. The concept of synthetic lethality, a genetic interaction in which the simultaneous loss of two genes or pathways that regulate a common essential process renders the cell nonviable, is a valuable tool for killing cancer cells that have known mutations. In this study, we conducted a synthetic lethality screen for compounds that specifically target SETD2-deficient cancer cells. The top hit, a compound called RITA, reduces cell viability and induces cell death only in the context of SETD2 loss, thereby highlighting a potential novel therapeutic strategy for treating SETD2-deficient cancers.

cell biology↗