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Hussain, J.

Publications and source records attributed to Hussain, J..

2 recordsLinked to original sources

Changes in peripheral sensory afference do not alter predictive motor planning: evidence from carpal tunnel syndrome

Anticipatory control organises motor output prior to predictable perturbations and is expressed in multi-digit tasks as anticipatory synergy adjustments (ASAs), which coordinate digit forces before movement onset. Whether such feedforward coordination depends on peripheral sensory input remains unclear. Carpal tunnel syndrome provides a model of altered median nerve afference with within-subject restoration following surgical decompression. We quantified ASA onset and amplitude in eleven individuals with carpal tunnel syndrome performing a multi-finger grasp-and-release task before and three weeks after decompression surgery. Postoperatively, sensory function improved, and total grip force decreased significantly across task phases, indicating more efficient force regulation. In contrast, ASA onset timing and amplitude were unchanged. Equivalence testing confirmed that pre- and post-operative ASA measures fell within predefined bounds of practical equivalence. These findings demonstrate a central-peripheral dissociation: feedback-mediated grip force scaling is sensory-dependent and rapidly recalibrates following afferent restoration, whereas feedforward synergy coordination remains stable despite months of degraded peripheral input. The preserved ASA suggests that central motor planning circuits maintain anticipatory coordination through efferent copy or cerebellar-mediated internal models that do not require continuous peripheral recalibration. This resilience may reflect the brains ability to maintain predictive motor planning despite chronic sensory degradation, with implications for understanding compensatory mechanisms in peripheral neuropathies and the limits of sensory-dependent motor adaptation.

neuroscience↗

Mevalonate metabolites contribute to granulocyte chemotaxis and mortality in murine endotoxemia

Statins appear to dramatically increase sepsis survival but only when treatment is initiated prior to hospitalization. This implies that statins exhibit a delayed-onset pro-survival benefit in septic patients that results in clinical futility of statin-therapy for patients already diagnosed with sepsis. Identification of mechanisms that contribute to increased sepsis-survival following statin-pretreatment may reveal novel therapeutic targets that do not suffer similar delayed onset benefits. Statins are used to treat hypercholesterolemia and function by inhibiting the production of the rate-limiting metabolite mevalonate. This indirectly inhibits the de novo synthesis of not only cholesterol but also isoprenoids that are involved in prenylation, the post-translational lipid modification of proteins. Mirroring clinical observations, chronic but not acute treatment with simvastatin significantly increased survival in a murine endotoxemia model. This was associated with reduced systemic granulocyte chemotaxis that occurred in a cell-intrinsic manner. In vitro modeling showed that simvastatin abolished chemoattractant responses and that this could be reversed by restoring geranylgeranyl pyrophosphate (GGPP) but not farnesyl pyrophosphate (FPP) nor cholesterol. Treatment with prenyltransferase inhibitors showed that chemoattractant responses were dependent on geranylgeranylation. Proteomic analysis of C15AlkOPP-prenylated proteins identified geranylgeranylated proteins involved in chemoattractant responses, including RHOA, RAC1, CDC42, and GNG2. Given the kinetic problems with initiating statin treatment after sepsis onset, prenyltransferases and geranylgeranylated proteins, such as RAC1 and GNG2, are promising interventional candidates for sepsis and critical inflammatory illness.

immunology↗