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Biology subjects

Henning, C.

Publications and source records attributed to Henning, C..

4 recordsLinked to original sources

Neural tracking of biological motion rhythms in early infancy: links to caregiver touch-related behaviours and attitudes

Infant environments are rich in rhythms, many of which are social in nature. These rhythms are proposed to play an important role in early communication and interpersonal synchrony. In this cross-sectional electroencephalography (EEG) study with 3- and 6-month-olds (n=31 and n=30, respectively), we examined whether the infant brain tracks the rhythmicity of locomotion-related biological motion in the visual domain and which experiential factors relate to this ability. We found robust neural tracking of biological motion rhythms at both ages, with no effects of age or orientation (upright or inverted). Additionally, we found that caregiver-reported practice of infant carrying/babywearing and caregiver attitudes toward social touch were linked to infant neural tracking of biological motion rhythms, particularly in the inverted condition. Finally, exploratory analyses revealed a lateralisation effect, whereby the left hemisphere processed rightward (vs. leftward) biological motion rhythms more strongly. Our findings suggest that from early on, the infant brain tracks the rhythmicity of whole-body biological motion. Furthermore, caregiver touch-related practices, particularly infant carrying/babywearing, may play a role in infant neural tracking of socially-relevant rhythms.

neuroscience↗

Population-level neural correlates of flexible avoidance learning in medial prefrontal cortex

The medial prefrontal cortex (mPFC) has been proposed to link sensory inputs and behavioral outputs to mediate the execution of learned behaviors. However, how such a link is implemented has remained unclear. To measure prefrontal neural correlates of sensory stimuli and learned behaviors, we performed population calcium imaging during a novel tone-signaled active avoidance paradigm in mice. We developed a novel analysis approach based on dimensionality reduction and decoding that allowed us to identify and isolate population activity patterns related the tone stimulus, learned avoidance actions and general motion. While tone-related activity was not informative about behavior, avoidance-related activity was predictive of upcoming avoidance actions. Moreover, avoidance-related activity distinguished between two different learned avoidance actions, consistent with a model in which mPFC contributes to the selection between different goal-directed actions. Overall, our results suggest that mPFC circuit dynamics transform sensory inputs into specific behavioral outputs through distributed population-level computations.

neuroscience↗

Synchronized infection identifies early rate-limiting steps in the hepatitis B virus life cycle.

Hepatitis B virus (HBV) is an enveloped DNA virus that contains a partially double-stranded relaxed circular (rc) DNA. Upon infection, rcDNA is delivered to the nucleus where it is repaired to covalently closed circular (ccc) DNA that serves as the transcription template for all viral RNAs. Our understanding of HBV particle entry dynamics and host pathways regulating intracellular virus trafficking and cccDNA formation is limited. The discovery of sodium taurocholate co-transporting peptide (NTCP) as the primary receptor allows studies on these early steps in viral life cycle. We employed a synchronized infection protocol to quantify HBV entry kinetics. HBV attachment to cells at 4{degrees}C is independent of NTCP, however, subsequent particle uptake is NTCP-dependent and reaches saturation at 12h post-infection. HBV uptake is clathrin- and dynamin dependent with actin and tubulin playing a role in the first 6h of infection. Cellular fractionation studies demonstrate HBV DNA in the nucleus within 6h of infection and cccDNA was first detected at 24h post-infection. Our studies show the majority (83%) of cell bound particles enter HepG2-NTCP cells, however, only a minority (<1%) of intracellular rcDNA was converted to cccDNA, highlighting this as a rate-limiting in establishing infection in vitro. This knowledge highlights the deficiencies in our in vitro cell culture systems and will inform the design and evaluation of physiologically relevant models that support efficient HBV replication.

microbiology↗

An in vivo inflammatory loop potentiates KRAS blockade

KRAS inhibitors perform inferior to other targeted drugs. To investigate a possible reason for this, we treated cancer cells with KRAS inhibitors deltarasin (targeting phosphodiesterase-{delta}), cysmethynil (targeting isoprenylcysteine carboxylmethyltransferase), and AA12 (targeting KRASG12C), and silenced/overexpressed mutant KRAS using custom vectors. We show that KRAS-mutant tumor cells exclusively respond to KRAS blockade in vivo, because the oncogene co-opts host myeloid cells via a C-C-motif chemokine ligand 2/interleukin-1{beta} signaling loop for sustained tumorigenicity. Indeed, KRAS-mutant tumors did not respond to deltarasin in Ccr2 and Il1b gene-deficient mice, but were deltarasin-sensitive in wild-type and Ccr2-deficient mice adoptively transplanted with wild-type murine bone marrow. A KRAS-dependent pro-inflammatory transcriptome was prominent in human cancers with high KRAS mutation prevalence and predicted poor survival. Hence the findings support that in vitro systems are suboptimal for anti-KRAS drug screens, and suggest that interleukin-1{beta} blockade might be specific for KRAS-mutant cancers.

cancer biology↗