Biology subjects

Cross, K.

Publications and source records attributed to Cross, K..

4 recordsLinked to original sources

bioRxiv2026

Dopaminergic tone predicts rhythmic temporal attention in Parkinson's disease

Beat perception, the ability to perceive and anticipate a regular pulse in music, is thought to depend on the basal ganglia. Dopaminergic signaling is a candidate mechanism given its prominence in basal ganglia circuitry and established function in encoding temporal predictions. Parkinson's disease (PD) provides a model for studying dopaminergic contributions to beat perception. To test the hypothesis that higher dopaminergic tone is associated with better beat perception, we conducted a study in PD patients (n=55) and matched controls (n=53). Participants performed a musical beat perception task, the Beat Drop Alignment Test (BDAT). They also completed a non-timing control task measuring musical pitch perception, the Mistuning Perception Test (MPT). We identified a double dissociation in PD patients: daily dopamine dose was associated with beat perception (r=.37, p=.005) but not pitch perception (r=.12, p=.397), while musical background was associated with pitch perception (r=.55, p<.001) but not beat perception (r=.16, p=.236). Results remained consistent when controlling for disease duration and age. This dissociation suggests the effect of dopamine is specific to beat perception and not reflective of a general improvement in auditory processing. High-dopamine patients outperformed both low-dopamine patients and age-matched controls, and this difference was driven by better detection of on-beat than off-beat events. Together, these results suggest that dopamine is associated with enhanced beat perception, potentially through modulation of temporal attention to expected beat times.

neuroscience↗

bioRxiv2023

Germline-targeting SOSIP trimer immunization elicits precursor CD4 binding-site targeting broadly neutralizing antibodies in infant macaques.

A vaccine that can achieve protective immunity prior to sexual debut is critical to prevent the estimated 410,000 new HIV infections that occur yearly in adolescents. As children living with HIV can make broadly neutralizing antibody (bnAb) responses in plasma at a faster rate than adults, early childhood is an opportune window for implementation of a multi-dose HIV immunization strategy to elicit protective immunity prior to adolescence. Therefore, the goal of our study was to assess the ability of a B cell lineage-designed HIV envelope SOSIP to induce bnAbs in early life. Infant rhesus macaques (RMs) received either BG505 SOSIP or the germline-targeting BG505 GT1.1 SOSIP (n=5/group) with the 3M-052-SE adjuvant at 0, 6, and 12 weeks of age. All infant RMs were then boosted with the BG505 SOSIP at weeks 26, 52 and 78, mimicking a pediatric immunization schedule of multiple vaccine boosts within the first two years of life. Both immunization strategies induced durable, high magnitude binding antibodies and plasma autologous virus neutralization that primarily targeted the CD4-binding site (CD4bs) or C3/465 epitope. Notably, three BG505 GT1.1-immunized infants exhibited a plasma HIV neutralization signature reflective of VRC01-like CD4bs bnAb precursor development and heterologous virus neutralization. Finally, infant RMs developed precursor bnAb responses at a similar frequency to that of adult RMs receiving a similar immunization strategy. Thus, a multi-dose immunization regimen with bnAb lineage designed SOSIPs is a promising strategy for inducing protective HIV bnAb responses in childhood prior to adolescence when sexual HIV exposure risk begins.

immunology↗

bioRxiv2019

Keep your hands apart: independent representations of ipsilateral and contralateral forelimbs in primary motor cortex

It is generally accepted that each cortical hemisphere primarily drives the opposite side of the body. Yet, primary motor cortical (M1) activity has been robustly correlated with both contralateral and ipsilateral arm movements. It has remained unanswered as to why ipsilaterally-related activity does not cause contralateral motor activity. Here we apply multi-joint elbow and shoulder loads to the left or right arms of monkeys during a postural perturbation task. We show that many M1 neurons respond to mechanical disturbances applied to either the contra- or ipsilateral arms. More neurons respond to loads applied to the contralateral arm with response magnitudes that were ~2x as large and had onset times that were ~10ms earlier. However, in some cases, neurons exhibited large and earlier responses to loads applied to the ipsilateral arm than loads applied to the contralateral arm. Similar effects were observed when the monkeys were maintaining postural control well after the load had been applied. Importantly, we show that the load preference to one arm has little predictive power on a neurons preference in the opposite arm. Furthermore, we found contralateral and ipsilateral neural activity resided in orthogonal subspaces allowing for a weighted sum of neural responses to extract the contralateral activity without interference from the ipsilateral activity, and vice versa. These data show how activity in M1 unrelated to downstream motor targets can be segregated from downstream motor output.

neuroscience↗

bioRxiv2019

Comparative genomics guides elucidation of vitamin B12 biosynthesis in novel human associated Akkermansia

BackgroundAkkermansia muciniphila is a mucin-degrading bacterium found in the gut of most healthy humans and is considered a next-generation probiotic. However, knowledge of the genomic and physiological diversity of human associated Akkermansia is limited, as only one species has been formally described. ResultsTo begin to fill this knowledge gap, we reconstructed 35 high-quality metagenome assembled genomes from children and combined them with 40 other publicly available genomes from adults and mice for comparative genomic analysis. We identified at least four species-level phylogroups (AmI-AmIV) with distinct functional potentials. Most notably, we identified the presence of putative cobalamin (vitamin B12) biosynthesis genes within the AmII (n=26/28) and AmIII (n=2/2) phylogroups. To test these predictions, 10 novel strains of Akkermansia were isolated from adults and screened for essential vitamin B12 biosynthesis genes via PCR. Two strains of the AmII phylogroup were positive for the presence of vitamin B12 biosynthesis genes, while all AmI strains, including the type strain A. muciniphila MucT, were negative. To demonstrate vitamin B12 biosynthesis, we measured the production of acetate, succinate, and propionate in the presence and absence of vitamin supplementation in representative strains of the AmI and AmII phylogroups since cobalamin is a cofactor in propionate metabolism. Results show that the Akkermansia AmII strain produced acetate and propionate in the absence of supplementation, which is indicative of de novo vitamin B12 biosynthesis. In contrast, acetate and succinate were the main fermentation products for the AmI strains when vitamin B12 was not supplied in the culture medium. ConclusionsWe identified Akkermansia strains as potentially important vitamin B12 biosynthetic bacteria in the human gut. This novel physiological trait of human associated Akkermansia may impact how these bacteria interact with the human host and other members of the human gut microbiome.

genomics↗