Early visual deprivation is known to have profound consequences on the subsequent development of spatial visual processing. However, its impact on temporal processing is not well characterized. We have examined spatial and temporal contrast sensitivity functions following treatment for early and extended bilateral visual deprivation in fifteen children born with congenital cataracts in rural India. The results reveal a marked difference in post-treatment spatial and temporal sensitivities. Whereas spatial processing in newly sighted children is significantly impaired relative to age-matched controls, temporal processing exhibits remarkable resilience and is comparable to that in the control group. This difference in spatial and temporal outcomes is especially surprising given our computational analyses of video sequences which indicate a strong linkage between the spatial and temporal spectral content of natural visual inputs. We consider possible explanations for this discrepancy.

Recognizing the limitations of standard vision assessments in capturing the real-world capabilities of individuals with low vision, we investigated the potential of the Seguin Form Board Test (SFBT), a widely-used intelligence assessment employing a visuo-haptic shape-fitting task, as an estimator of vision's practical utility. We present findings from 23 children from India, who underwent treatment for congenital bilateral dense cataracts, and 21 control participants. To assess the development of functional visual ability, we conducted the SFBT and the standard measure of visual acuity, before and longitudinally after treatment. We observed a dissociation in the development of shape-fitting and visual acuity. Improvements of patients' shape-fitting preceded enhancements in their visual acuity after surgery and emerged even with acuity worse than that of control participants. Our findings highlight the importance of incorporating multi-modal and cognitive aspects into evaluations of visual proficiency in low-vision conditions, to better reflect vision's impact on daily activities.

Aberrations in nuclear size and shape are commonly used to identify cancerous tissue. However, it remains unclear whether the disturbed nuclear structure directly contributes to the cancer pathology or is merely a consequence of other events occurring during tumorigenesis. Here, we show that highly invasive and proliferative breast cancer cells frequently exhibit Akt-driven lower expression of the nuclear envelope proteins lamin A/C, leading to increased nuclear deformability that permits enhanced cell migration through confined environments that mimic interstitial spaces encountered during metastasis. Importantly, increasing lamin A/C expression in highly invasive breast cancer cells reflected gene expression changes characteristic of human breast tumors with higher LMNA expression, and specifically affected pathways related to cell-ECM interactions, cell metabolism, and PI3K/Akt signaling. Further supporting an important role of lamins in breast cancer metastasis, analysis of lamin levels in human breast tumors revealed a significant association between lower lamin A levels, Akt signaling, and decreased disease-free survival. These findings suggest that downregulation of lamin A/C in breast cancer cells may influence both cellular physical properties and biochemical signaling to promote metastatic progression.

Chromosomal instability is a hallmark of cancer that results from ongoing errors in chromosome segregation during mitosis. Although chromosomal instability is a major driver of tumour evolution, its role in metastasis has not been established. Here we show that chromosomal instability promotes metastasis by sustaining a tumour cell-autonomous response to cytosolic DNA. Errors in chromosome segregation create a preponderance of micronuclei whose rupture spills genomic DNA into the cytosol. This leads to the activation of the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) cytosolic DNA-sensing pathway and downstream noncanonical NF-κB signalling. Genetic suppression of chromosomal instability markedly delays metastasis even in highly aneuploid tumour models, whereas continuous chromosome segregation errors promote cellular invasion and metastasis in a STING-dependent manner. By subverting lethal epithelial responses to cytosolic DNA, chromosomally unstable tumour cells co-opt chronic activation of innate immune pathways to spread to distant organs.