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Luff, S.

Publications and source records attributed to Luff, S..

3 recordsLinked to original sources

Rapid phase resetting of Aedes aegypti circadian rhythms by transient alterations in light exposure

Circadian clocks enable mosquitoes to anticipate recurring environmental variations and coordinate behaviors critical for survival and disease transmission, such as locomotion, reproduction, host-seeking, and blood-feeding, with times of day when performance is maximal. In Aedes aegypti, locomotor activity follows a robust diurnal rhythm shaped by endogenous circadian clocks and environmental cues, among which light has been shown to be the primary source of temporal information. While early studies established the role of light in regulating locomotor activity, behavior, oviposition and pupation, it remains unclear which features of a light cycle drive changes in circadian rhythms. This question is increasingly relevant as Ae. aegypti is frequently exposed to artificial and dynamic lighting conditions in urban environments. Here, we investigated how transient changes in light schedules influence circadian rhythms in locomotor activity by systematically manipulating the timing, duration, and direction of light exposure. Using a high-throughput assay, we tested over 1900 individuals, including wild-type and timeless knockout mutants, and showed that a single day of al tered lighting is sufficient to induce robust phase shifts, with no evidence of masking effects. A 6-hour light pulse was sufficient to re-entrain mosquitoes regardless of the timing of the pulse, and phase shifts were primarily driven by the offset time of the light pulse, indicating that light-offset acts as a major zeitgeber. Together, these findings challenge conventional assumptions about the timescale of circadian synchronization and highlight the remarkable plasticity of mosquito behavior in response to anthropogenic light. Eventually, these effects could explain the rapid adaptation of the species to urban environments and have potential consequences for disease transmission dynamics.

animal behavior and cognition↗

Temporal synchrony between human odor rhythms and mosquito olfactory preference shapes host attraction

For anthropophilic mosquitoes such as Aedes aegypti, aligning host-seeking with human availability enhances foraging efficiency and reproductive success. Although time of day modulates mosquito activity and olfactory sensitivity, it remains unknown whether human hosts display rhythmic changes in odor cues and whether mosquitoes adjust their sensory responses accordingly. Here, we combine chemical, behavioral, genetic, and transcriptomic approaches to reveal that both mosquitoes and their human hosts in this interaction are temporally synchronized. Gas chromatography-mass spectrometry showed systematic daily shifts in human body odor composition between morning and evening. Correspondingly, mosquitoes prefer host odors that match their own active phase--a time-specific preference abolished in timeless mutants and under constant darkness. Silencing the timeless gene further induced an aversion for the host scent under light-dark conditions. Transcriptomic analysis of mosquito heads and antennae uncovered rhythmic expression of sensory and neuromodulatory genes, driven by both circadian and light-dark cycles and which peaks during mosquitoes active periods, with rhythmic co-expression networks collapsing in timeless knockouts. Together, these results show that mosquito attraction to humans is temporally tuned by the interplay of host odor rhythms and mosquito sensory rhythms, revealing a previously unrecognized form of interspecific temporal synchronization in vector-host interactions.

animal behavior and cognition↗

WNT signaling in human pluripotent stem cells promotes HDAC2-dependent epigenetic programs and development of retinoic acid-responsive mesoderm

Human pluripotent stem cells (hPSCs) can be used as a scalable source of lymphocytes for adoptive cell therapies, contingent on the robust generation of definitive hematopoietic intermediates. Early WNT activation with CHIR99021 during mesoderm induction promoted the formation of KDR+ ALDH1A2+ mesodermal progenitors and subsequent generation of T cells in a retinoic acid (RA)-dependent manner. Integrated scRNA-seq and ATAC-seq defined a WNT-dependent developmental trajectory from hPSCs to KDR+ ALDH1A2+ mesoderm. Gene regulatory network modeling predicted HDAC2 and E-box transcription factors as regulators of RA-responsive mesodermal differentiation downstream of WNT. HDAC2 knockout impaired, while HDAC2 overexpression enhanced, KDR+ ALDH1A2+ progenitor formation. E-box factor manipulation had no discernible effect. An orthogonal chemical screen confirmed that HDAC2 inhibition suppressed KDR+ ALDH1A2+ mesodermal progenitors, whereas modulating histone methylation enhanced their formation. These findings reveal mechanisms by which WNT signaling promotes RA-responsive mesoderm and suggest methods to improve the generation of lymphocytes from hPSCs.

developmental biology↗