Hmga2 is dispensable for pancreatic cancer development, metastasis, and therapy resistance.

Expression of the chromatin-associated protein HMGA2 correlates with progression, metastasis and therapy resistance in pancreatic ductal adenocarcinoma (PDAC). Hmga2 has also been identified as a marker of a transient subpopulation of PDAC cells that has increased metastatic ability. Here, we characterize the requirement for Hmga2 during growth, dissemination, and metastasis of PDAC in vivo using conditional inactivation of Hmga2 in well-established autochthonous mouse models of PDAC. Overall survival, primary tumour burden, presence of disseminated tumour cells in the peritoneal cavity or circulating tumour cells in the blood, and presence and number of metastases were not significantly different between mice with Hmga2-wildtype or Hmga2-deficient tumours. Treatment of mice with Hmga2-wildtype and Hmga2-deficient tumours with gemcitabine did not uncover a significant impact of Hmga2-deficiency on gemcitabine sensitivity. Hmga1 and Hmga2 overlap in their expression in both human and murine PDAC, however knockdown of Hmga1 in Hmga2-deficient cancer cells also did not decrease metastatic ability. Thus, Hmga2 remains a prognostic marker which identifies a metastatic cancer cell state in primary PDAC, however Hmga2 has limited if any direct functional impact on PDAC progression and therapy resistance

Neural correlates of differential finger gesture imitation deficits in left hemisphere stroke

Behavioural studies in apraxic patients revealed dissociations between the processing of meaningful (MF) and meaningless (ML) gestures. Consequently, the existence of two differential neural mechanisms for the imitation of either gesture type has been postulated. While the indirect (semantic) route exclusively enables the imitation of MF gestures, the direct route can be used for the imitation of any gesture type, irrespective of meaning, and thus especially for ML gestures. Concerning neural correlates, it is debated which of the visuo-motor streams (i.e., the ventral steam, the ventro-dorsal stream, or the dorso-dorsal stream) supports the postulated indirect and direct imitation routes.To probe the hypotheses that regions of the dorso-dorsal stream are involved differentially in the imitation of ML gestures and that regions of the ventro-dorsal stream are involved differentially in the imitation of MF gestures, we analysed behavioural (imitation of MF and ML finger gestures) and lesion data of 293 patients with a left hemisphere (LH) stroke.Confirming previous work, the current sample of LH stroke patients imitated MF finger gestures better than ML finger gestures. The analysis using voxel-based lesion symptom mapping (VLSM) revealed that LH damage to dorso-dorsal stream areas was associated with an impaired imitation of ML finger gestures, whereas damage to ventro-dorsal regions was associated with a deficient imitation of MF finger gestures.Accordingly, the analyses of the imitation of visually uniform and thus highly comparable MF and ML finger gestures support the dual-route model for gesture imitation at the behavioural and lesion level in a substantial patient sample. Furthermore, the data show that the direct route for ML finger gesture imitation depends on the dorso-dorsal visuo-motor stream while the indirect route for MF finger gesture imitation is related to regions of the ventro-dorsal visuo-motor stream

Hmga2 is dispensable for pancreatic cancer development, metastasis, and therapy resistance.

Expression of the chromatin-associated protein HMGA2 correlates with progression, metastasis and therapy resistance in pancreatic ductal adenocarcinoma (PDAC). Hmga2 has also been identified as a marker of a transient subpopulation of PDAC cells that has increased metastatic ability. Here, we characterize the requirement for Hmga2 during growth, dissemination, and metastasis of PDAC in vivo using conditional inactivation of Hmga2 in well-established autochthonous mouse models of PDAC. Overall survival, primary tumour burden, presence of disseminated tumour cells in the peritoneal cavity or circulating tumour cells in the blood, and presence and number of metastases were not significantly different between mice with Hmga2-wildtype or Hmga2-deficient tumours. Treatment of mice with Hmga2-wildtype and Hmga2-deficient tumours with gemcitabine did not uncover a significant impact of Hmga2-deficiency on gemcitabine sensitivity. Hmga1 and Hmga2 overlap in their expression in both human and murine PDAC, however knockdown of Hmga1 in Hmga2-deficient cancer cells also did not decrease metastatic ability. Thus, Hmga2 remains a prognostic marker which identifies a metastatic cancer cell state in primary PDAC, however Hmga2 has limited if any direct functional impact on PDAC progression and therapy resistance

Neural correlates of differential finger gesture imitation deficits in left hemisphere stroke

Behavioural studies in apraxic patients revealed dissociations between the processing of meaningful (MF) and meaningless (ML) gestures. Consequently, the existence of two differential neural mechanisms for the imitation of either gesture type has been postulated. While the indirect (semantic) route exclusively enables the imitation of MF gestures, the direct route can be used for the imitation of any gesture type, irrespective of meaning, and thus especially for ML gestures. Concerning neural correlates, it is debated which of the visuo-motor streams (i.e., the ventral steam, the ventro-dorsal stream, or the dorso-dorsal stream) supports the postulated indirect and direct imitation routes. To probe the hypotheses that regions of the dorso-dorsal stream are involved differentially in the imitation of ML gestures and that regions of the ventro-dorsal stream are involved differentially in the imitation of MF gestures, we analysed behavioural (imitation of MF and ML finger gestures) and lesion data of 293 patients with a left hemisphere (LH) stroke. Confirming previous work, the current sample of LH stroke patients imitated MF finger gestures better than ML finger gestures. The analysis using voxel-based lesion symptom mapping (VLSM) revealed that LH damage to dorso-dorsal stream areas was associated with an impaired imitation of ML finger gestures, whereas damage to ventro-dorsal regions was associated with a deficient imitation of MF finger gestures. Accordingly, the analyses of the imitation of visually uniform and thus highly comparable MF and ML finger gestures support the dual-route model for gesture imitation at the behavioural and lesion level in a substantial patient sample. Furthermore, the data show that the direct route for ML finger gesture imitation depends on the dorso-dorsal visuo-motor stream while the indirect route for MF finger gesture imitation is related to regions of the ventro-dorsal visuo-motor stream

Same data, different analysts: variation in effect sizes due to analytical decisions in ecology and evolutionary biology

Gould E, Fraser H, Parker T, et al. Same data, different analysts: variation in effect sizes due to analytical decisions in ecology and evolutionary biology. 2023.Although variation in effect sizes and predicted values among studies of similar phenomena is inevitable, such variation far exceeds what might be produced by sampling error alone. One possible explanation for variation among results is differences among researchers in the decisions they make regarding statistical analyses. A growing array of studies has explored this analytical variability in different (mostly social science) fields, and has found substantial variability among results, despite analysts having the same data and research question. We implemented an analogous study in ecology and evolutionary biology, fields in which there have been no empirical exploration of the variation in effect sizes or model predictions generated by the analytical decisions of different researchers. We used two unpublished datasets, one from evolutionary ecology (blue tit, Cyanistes caeruleus, to compare sibling number and nestling growth) and one from conservation ecology (Eucalyptus, to compare grass cover and tree seedling recruitment), and the project leaders recruited 174 analyst teams, comprising 246 analysts, to investigate the answers to prespecified research questions. Analyses conducted by these teams yielded 141 usable effects for the blue tit dataset, and 85 usable effects for the Eucalyptus dataset. We found substantial heterogeneity among results for both datasets, although the patterns of variation differed between them. For the blue tit analyses, the average effect was convincingly negative, with less growth for nestlings living with more siblings, but there was near continuous variation in effect size from large negative effects to effects near zero, and even effects crossing the traditional threshold of statistical significance in the opposite direction. In contrast, the average relationship between grass cover and Eucalyptus seedling number was only slightly negative and not convincingly different from zero, and most effects ranged from weakly negative to weakly positive, with about a third of effects crossing the traditional threshold of significance in one direction or the other. However, there were also several striking outliers in the Eucalyptus dataset, with effects far from zero. For both datasets, we found substantial variation in the variable selection and random effects structures among analyses, as well as in the ratings of the analytical methods by peer reviewers, but we found no strong relationship between any of these and deviation from the meta-analytic mean. In other words, analyses with results that were far from the mean were no more or less likely to have dissimilar variable sets, use random effects in their models, or receive poor peer reviews than those analyses that found results that were close to the mean. The existence of substantial variability among analysis outcomes raises important questions about how ecologists and evolutionary biologists should interpret published results, and how they should conduct analyses in the future