Is object-based warping solely object-based?

Object-based warping is a visual illusion in which dots appear farther apart from each other when superimposed on an object. Previous research found that the illusion's strength varies with the perceived objecthood of the display. We tested whether objecthood alone determines the strength of the visual illusion or if low-level factors separable from objecthood also play a role. In Experiments 1-2, we varied low-level features to assess their impact on the warping illusion. We found that the warping illusion is equally strong for a variety of shapes but varies with the elements by which shape is defined. Shapes composed of continuous edges produced larger warping effects than shapes defined by disconnected elements. In Experiment 3, we varied a display's objecthood while holding low-level features constant. Displays with matched low-level features produced warping effects of the same size even when the perceived unity of the elements in the display varied. In Experiments 4-6, we tested whether displays with low-level features predicted to be important in spatial warping produced the visual illusion even when the display weakly configured into a single object. Results showed that the presence of low-level features like contour solidity and convexity determined warping effect sizes over and above what could be accounted for by the display's perceived objecthood. Our findings challenge the view that the spatial warping illusion is solely object-based. Other factors like the solidity of contours and contours' position relative to reference dots appear to play separate and important roles in determining warping effect sizes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Founding the Wnt gene family: How wingless was found to be a positional signal and oncogene homolog.

The Wnt family of developmental regulators were named after the Drosophila segmentation gene wingless and the murine proto-oncogene int-1. Homology between these two genes connected oncogenesis to cell-cell signals in development. I review how wingless was initially characterized, and cloned, as part of the quest to identify developmental cell-to-cell signals, based on predictions of the Positional Information Model, and on the properties of homeotic and segmentation gene mutants. The requirements and cell-nonautonomy of wingless in patterning multiple embryonic and adult structures solidified its status as a candidate signaling molecule. The physical location of wingless mutations and transcription unit defined the gene and its developmental transcription pattern. When the Drosophila homolog of int-1 was then isolated, and predicted to encode a secreted proto-oncogene homolog, it's identity to the wingless gene confirmed that a developmental cell-cell signal had been identified and connected cancer to development.

For deep networks, the whole equals the sum of the parts.

Deep convolutional networks exceed humans in sensitivity to local image properties, but unlike biological vision systems, do not discover and encode abstract relations that capture important properties of objects and events in the world. Coupling network architectures with additional machinery for encoding abstract relations will make deep networks better models of human abilities and more versatile and capable artificial devices.

Protocol for assessing translation in living Drosophila imaginal discs by O-propargyl-puromycin incorporation.

Translation is a fundamental process of cellular behavior. Here, we present a protocol for measuring translation in Drosophila epithelial tissues using O-propargyl-puromycin (OPP), a puromycin derivative. We detail steps for larval dissection, OPP incorporation, fixation, OPP labeling, immunostaining, and imaging. We also provide details of quantification analysis. Significantly, OPP addition to methionine-containing media enables polypeptide labeling in living cells. Here, we study wing imaginal discs, an excellent model system for investigating growth, proliferation, pattern formation, differentiation, and cell death. For complete details on the use and execution of this protocol, please refer to Lee et al. (2018), Ji et al. (2019), and Kiparaki et al. (2022).1,2,3.

Ribosomal protein mutations and cell competition: autonomous and nonautonomous effects on a stress response.

Ribosomal proteins (Rps) are essential for viability. Genetic mutations affecting Rp genes were first discovered in Drosophila, where they represent a major class of haploinsufficient mutations. One mutant copy gives rise to the dominant "Minute" phenotype, characterized by slow growth and small, thin bristles. Wild-type (WT) and Minute cells compete in mosaics, that is, Rp+/- are preferentially lost when their neighbors are of the wild-type genotype. Many features of Rp gene haploinsufficiency (i.e. Rp+/- phenotypes) are mediated by a transcriptional program. In Drosophila, reduced translation and slow growth are under the control of Xrp1, a bZip-domain transcription factor induced in Rp mutant cells that leads ultimately to the phosphorylation of eIF2α and consequently inhibition of most translation. Rp mutant phenotypes are also mediated transcriptionally in yeast and in mammals. In mammals, the Impaired Ribosome Biogenesis Checkpoint activates p53. Recent findings link Rp mutant phenotypes to other cellular stresses, including the DNA damage response and endoplasmic reticulum stress. We suggest that cell competition results from nonautonomous inputs to stress responses, bringing decisions between adaptive and apoptotic outcomes under the influence of nearby cells. In Drosophila, cell competition eliminates aneuploid cells in which loss of chromosome leads to Rp gene haploinsufficiency. The effects of Rp gene mutations on the whole organism, in Minute flies or in humans with Diamond-Blackfan Anemia, may be inevitable consequences of pathways that are useful in eliminating individual cells from mosaics. Alternatively, apparently deleterious whole organism phenotypes might be adaptive, preventing even more detrimental outcomes. In mammals, for example, p53 activation appears to suppress oncogenic effects of Rp gene haploinsufficiency.

Haploinsufficiency of the essential gene Rps12 causes defects in erythropoiesis and hematopoietic stem cell maintenance.

Ribosomal protein (Rp) gene haploinsufficiency can result in Diamond-Blackfan Anemia (DBA), characterized by defective erythropoiesis and skeletal defects. Some mouse Rp mutations recapitulate DBA phenotypes, although others lack erythropoietic or skeletal defects. We generated a conditional knockout mouse to partially delete Rps12. Homozygous Rps12 deletion resulted in embryonic lethality. Mice inheriting the Rps12KO/+ genotype had growth and morphological defects, pancytopenia, and impaired erythropoiesis. A striking reduction in hematopoietic stem cells (HSCs) and progenitors in the bone marrow (BM) was associated with decreased ability to repopulate the blood system after competitive and non-competitive BM transplantation. Rps12KO/+ lost HSC quiescence, experienced ERK and MTOR activation, and increased global translation in HSC and progenitors. Post-natal heterozygous deletion of Rps12 in hematopoietic cells using Tal1-Cre-ERT also resulted in pancytopenia with decreased HSC numbers. However, post-natal Cre-ERT induction led to reduced translation in HSCs and progenitors, suggesting that this is the most direct consequence of Rps12 haploinsufficiency in hematopoietic cells. Thus, RpS12 has a strong requirement in HSC function, in addition to erythropoiesis.

Independent mechanisms for processing local contour features and global shape.

The visual system can extract the global shape of an object from highly variable local contour features. We propose that there are separate systems for processing local and global shape. These systems are independent and process information differently. Global shape encoding accurately represents the form of low-frequency contour variations, whereas the local system encodes only summary statistics that describe typical features of high-frequency elements. In Experiments 1-4, we tested this hypothesis by obtaining same/different judgments for shapes that differed in local features, global features, or both. We found low sensitivity to changed local features that shared the same summary statistics, and no advantage in sensitivity for shapes that differed in both local and global features compared to shapes that differed only in global features. This sensitivity difference persisted when physical contour differences were equated and when shape feature sizes and exposure durations were increased. In Experiment 5, we compared sensitivity to sets of local contour features with matched or unmatched statistical properties. Sensitivity was higher for unmatched statistical properties than for properties sampled from the same statistical distribution. Experiment 6 directly tested our hypothesis of independent local and global systems using visual search. Search based on either local or global shape differences produced pop-out effects, but search for a target based on a conjunction of local and global differences required focal attention. These findings support the notion that separate mechanisms process local and global contour information and that the kinds of information these mechanisms encode are fundamentally different. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Comparison of robotic-assisted minimally invasive esophagectomy versus minimally invasive esophagectomy: A propensity-matched study from a single high-volume institution.

OBJECTIVE: Robotic-assisted minimally invasive esophagectomy accounts for a growing proportion of esophagectomies, potentially due to improved technical capabilities simplifying the challenging aspects of standard minimally invasive esophagectomy. However, there is limited evidence directly comparing both operations. The objective is to evaluate the short-term and long-term outcomes of robotic-assisted minimally invasive esophagectomy in comparison with the minimally invasive esophagectomy approach for patients with esophageal cancer over a 7-year period at a high-volume center. The primary end points of this study were overall survival and disease-free survival. Secondary end points included operation-specific morbidity, lymph node yield, readmission status, and in-hospital, 30-day, and 90-day mortality. METHODS: Patients who underwent robotic-assisted minimally invasive esophagectomy or standard minimally invasive esophagectomy over a 7-year period were identified from a prospectively maintained database. Inclusion criteria were patients with stage I to III disease, operations performed past the learning curve, and no evidence of scleroderma or cirrhosis. A 1:3 propensity match (robotic-assisted minimally invasive esophagectomy:minimally invasive esophagectomy) for multiple clinical covariates was performed to identify the final study cohort. Perioperative outcomes were compared between the 2 operations. RESULTS: A total of 734 patients undergoing minimally invasive esophagectomy (n = 630) or robotic-assisted minimally invasive esophagectomy (n = 104) for esophageal cancer were identified. After exclusions and matching, a total cohort of 246 patients undergoing robotic-assisted minimally invasive esophagectomy (n = 65) or minimally invasive esophagectomy (n = 181) were identified. There was no difference in overall survival (P = .69) or disease-free survival (P = .70). There were no significant differences in rates of major morbidity: pneumonia (17% vs 17%, P = .34), chylothorax (8% vs 9%, P = .95), recurrent laryngeal nerve injury (0% vs 1.5%, P = 1), anastomotic leak (5% vs 4%, P = .49), intraoperative complications (9% vs 8%, P = .73), or complete resection rates (99% vs 96%, P = .68). There was no difference in in-hospital (P = .89), 30-day (P = .66) or 90-day mortality (P = .73) between both cohorts. The robotic-assisted minimally invasive esophagectomy cohort yielded a higher median lymph node harvest in comparison with the minimally invasive esophagectomy cohort (32 vs 29, P = .02). CONCLUSIONS: Robotic-assisted minimally invasive esophagectomy may improve lymphadenectomy in patients undergoing esophagectomy for cancer. Minimally invasive esophagectomy and robotic-assisted minimally invasive esophagectomy are otherwise associated with similar mortality, morbidity, and perioperative outcomes. Further prospective study is required to investigate whether improved lymph node resection may translate to improved oncologic outcomes.

Reducing the aneuploid cell burden - cell competition and the ribosome connection.

Aneuploidy, the gain or loss of chromosomes, is the cause of birth defects and miscarriage and is almost ubiquitous in cancer cells. Mosaic aneuploidy causes cancer predisposition, as well as age-related disorders. Despite the cell-intrinsic mechanisms that prevent aneuploidy, sporadic aneuploid cells do arise in otherwise normal tissues. These aneuploid cells can differ from normal cells in the copy number of specific dose-sensitive genes, and may also experience proteotoxic stress associated with mismatched expression levels of many proteins. These differences may mark aneuploid cells for recognition and elimination. The ribosomal protein gene dose in aneuploid cells could be important because, in Drosophila, haploinsufficiency for these genes leads to elimination by the process of cell competition. Constitutive haploinsufficiency for human ribosomal protein genes causes Diamond Blackfan anemia, but it is not yet known whether ribosomal protein gene dose contributes to aneuploid cell elimination in mammals. In this Review, we discuss whether cell competition on the basis of ribosomal protein gene dose is a tumor suppressor mechanism, reducing the accumulation of aneuploid cells. We also discuss how this might relate to the tumor suppressor function of p53 and the p53-mediated elimination of aneuploid cells from murine embryos, and how cell competition defects could contribute to the cancer predisposition of Diamond Blackfan anemia.

The CRL4 E3 ligase Mahjong/DCAF1 controls cell competition through the transcription factor Xrp1, independently of polarity genes.

Cell competition, the elimination of cells surrounded by more fit neighbors, is proposed to suppress tumorigenesis. Mahjong (Mahj), a ubiquitin E3 ligase substrate receptor, has been thought to mediate competition of cells mutated for lethal giant larvae (lgl), a neoplastic tumor suppressor that defines apical-basal polarity of epithelial cells. Here, we show that Drosophila cells mutated for mahjong, but not for lgl [l(2)gl], are competed because they express the bZip-domain transcription factor Xrp1, already known to eliminate cells heterozygous for ribosomal protein gene mutations (Rp/+ cells). Xrp1 expression in mahj mutant cells results in activation of JNK signaling, autophagosome accumulation, eIF2α phosphorylation and lower translation, just as in Rp/+ cells. Cells mutated for damage DNA binding-protein 1 (ddb1; pic) or cullin 4 (cul4), which encode E3 ligase partners of Mahj, also display Xrp1-dependent phenotypes, as does knockdown of proteasome subunits. Our data suggest a new model of mahj-mediated cell competition that is independent of apical-basal polarity and couples Xrp1 to protein turnover.

Deep learning models fail to capture the configural nature of human shape perception.

A hallmark of human object perception is sensitivity to the holistic configuration of the local shape features of an object. Deep convolutional neural networks (DCNNs) are currently the dominant models for object recognition processing in the visual cortex, but do they capture this configural sensitivity? To answer this question, we employed a dataset of animal silhouettes and created a variant of this dataset that disrupts the configuration of each object while preserving local features. While human performance was impacted by this manipulation, DCNN performance was not, indicating insensitivity to object configuration. Modifications to training and architecture to make networks more brain-like did not lead to configural processing, and none of the networks were able to accurately predict trial-by-trial human object judgements. We speculate that to match human configural sensitivity, networks must be trained to solve a broader range of object tasks beyond category recognition.

The transcription factor Xrp1 orchestrates both reduced translation and cell competition upon defective ribosome assembly or function.

Ribosomal Protein (Rp) gene haploinsufficiency affects translation rate, can lead to protein aggregation, and causes cell elimination by competition with wild type cells in mosaic tissues. We find that the modest changes in ribosomal subunit levels observed were insufficient for these effects, which all depended on the AT-hook, bZip domain protein Xrp1. Xrp1 reduced global translation through PERK-dependent phosphorylation of eIF2α. eIF2α phosphorylation was itself sufficient to enable cell competition of otherwise wild type cells, but through Xrp1 expression, not as the downstream effector of Xrp1. Unexpectedly, many other defects reducing ribosome biogenesis or function (depletion of TAF1B, eIF2, eIF4G, eIF6, eEF2, eEF1α1, or eIF5A), also increased eIF2α phosphorylation and enabled cell competition. This was also through the Xrp1 expression that was induced in these depletions. In the absence of Xrp1, translation differences between cells were not themselves sufficient to trigger cell competition. Xrp1 is shown here to be a sequence-specific transcription factor that regulates transposable elements as well as single-copy genes. Thus, Xrp1 is the master regulator that triggers multiple consequences of ribosomal stresses and is the key instigator of cell competition.

Configural relations in humans and deep convolutional neural networks.

Deep convolutional neural networks (DCNNs) have attracted considerable interest as useful devices and as possible windows into understanding perception and cognition in biological systems. In earlier work, we showed that DCNNs differ dramatically from human perceivers in that they have no sensitivity to global object shape. Here, we investigated whether those findings are symptomatic of broader limitations of DCNNs regarding the use of relations. We tested learning and generalization of DCNNs (AlexNet and ResNet-50) for several relations involving objects. One involved classifying two shapes in an otherwise empty field as same or different. Another involved enclosure. Every display contained a closed figure among contour noise fragments and one dot; correct responding depended on whether the dot was inside or outside the figure. The third relation we tested involved a classification that depended on which of two polygons had more sides. One polygon always contained a dot, and correct classification of each display depended on whether the polygon with the dot had a greater number of sides. We used DCNNs that had been trained on the ImageNet database, and we used both restricted and unrestricted transfer learning (connection weights at all layers could change with training). For the same-different experiment, there was little restricted transfer learning (82.2%). Generalization tests showed near chance performance for new shapes. Results for enclosure were at chance for restricted transfer learning and somewhat better for unrestricted (74%). Generalization with two new kinds of shapes showed reduced but above-chance performance (≈66%). Follow-up studies indicated that the networks did not access the enclosure relation in their responses. For the relation of more or fewer sides of polygons, DCNNs showed successful learning with polygons having 3-5 sides under unrestricted transfer learning, but showed chance performance in generalization tests with polygons having 6-10 sides. Experiments with human observers showed learning from relatively few examples of all of the relations tested and complete generalization of relational learning to new stimuli. These results using several different relations suggest that DCNNs have crucial limitations that derive from their lack of computations involving abstraction and relational processing of the sort that are fundamental in human perception.

Activity-Based Cost Analysis of Robotic Anatomic Lung Resection During Program Implementation.

BACKGROUND: While robotic-assisted lung resection has seen a significant rise in adoption, concerns remain regarding initial programmatic outcomes and potential increased costs. We present our initial outcomes and cost analysis since initiation of a robotic lung resection program. METHODS: Patients undergoing either video-assisted thoracoscopic lobectomy or segmentectomy (VATS) or robotic-assisted lobectomy or segmentectomy (RALS) between August of 2014 and January of 2017 underwent retrospective review. Patients underwent 1:1 propensity matching based on preoperative characteristics. Perioperative and 30-day outcomes were compared between groups. Detailed activity-based costing analysis was performed on individual patient encounters taking into effect direct and indirect controllable costs, including robotic operative supplies. RESULTS: There were no differences in 30-day mortality between RALS (n = 74) and VATS (n = 74) groups (0% vs 1.4%; P = 1). RALS patients had a decreased median length of stay (4 days vs 7 days; P < .001) and decreased median chest tube duration (3 days vs 5 days, P < .001). Total direct costs, including direct supply costs, were not significantly different between RALS and VATS ($6621 vs $6483; P = .784). Median total operating costs and total unit support costs, which are closely correlated to length of stay, were lower in the RALS group. Overall median controllable costs were significantly different between RALS and VATS ($16,352 vs $21,154; P = .025). CONCLUSIONS: A potentially cost-advantageous robotic-assisted pulmonary resection program can be initiated within the context of an existing minimally invasive thoracic surgery program while maintaining good clinical outcomes when compared with traditional VATS. Process-of-care changes associated with RALS may account for decreased costs in this setting.

Constant curvature modeling of abstract shape representation.

How abstract shape is perceived and represented poses crucial unsolved problems in human perception and cognition. Recent findings suggest that the visual system may encode contours as sets of connected constant curvature segments. Here we describe a model for how the visual system might recode a set of boundary points into a constant curvature representation. The model includes two free parameters that relate to the degree to which the visual system encodes shapes with high fidelity vs. the importance of simplicity in shape representations. We conducted two experiments to estimate these parameters empirically. Experiment 1 tested the limits of observers' ability to discriminate a contour made up of two constant curvature segments from one made up of a single constant curvature segment. Experiment 2 tested observers' ability to discriminate contours generated from cubic splines (which, mathematically, have no constant curvature segments) from constant curvature approximations of the contours, generated at various levels of precision. Results indicated a clear transition point at which discrimination becomes possible. The results were used to fix the two parameters in our model. In Experiment 3, we tested whether outputs from our parameterized model were predictive of perceptual performance in a shape recognition task. We generated shape pairs that had matched physical similarity but differed in representational similarity (i.e., the number of segments needed to describe the shapes) as assessed by our model. We found that pairs of shapes that were more representationally dissimilar were also easier to discriminate in a forced choice, same/different task. The results of these studies provide evidence for constant curvature shape representation in human visual perception and provide a testable model for how abstract shape descriptions might be encoded.

Autotransplantation as a feasible intervention for combined nutcracker syndrome and Loin Pain Hematuria Syndrome.

Anterior Nutcracker Syndrome (NCS) can occur when the aorta and superior mesenteric artery compress the left renal vein. Loin pain hematuria syndrome (LPHS) occurs as kidney pain resulting from a past insult to the kidney, most commonly from nephrolithiasis. We herein present a case of previously treated NCS. Three months after treatment with GVT, the pelvic congestion was resolved but left flank pain continued concerning for undiagnosed Loin Pain Hematuria. Additionally, we present a treatment algorithm that provides a differential pathway for diagnosis and treatment of combined NCS and LPHS.

Robotic-assisted Kidney Transplantation With Simultaneous Bilateral Nephrectomies Is an Efficient, Feasible, and Safe Way to Manage Patients With Renal Failure Secondary to Adult Polycystic Kidney Disease.

Kidney transplantation has become the standard of care for end-stage renal disease secondary to adult polycystic kidney disease. Open surgical techniques remain the gold standard, although minimally invasive methods have gained traction in recent years. Native nephrectomy is frequently needed secondary to size or symptoms. Continued developments in surgical technology have allowed for the introduction of computer-assisted surgery (Robotics). We aim to describe the feasibility, safety, and efficiency of simultaneous laparoscopic bilateral nephrectomy and robotic-assisted kidney transplantation to treat end-stage renal kidney transplantation secondary to polycystic kidney disease. In this initial experience, 3 patients underwent kidney transplantation with a simultaneous bilateral nephrectomy. All patients tolerated the procedure well with no postoperative blood transfusions, dialysis, or surgical site infections. Simultaneous laparoscopic bilateral nephrectomy and robotic-assisted kidney transplantation may be feasible, safe, and efficient techniques. Complications were minimal, with short hospital stays. Supplemental Video; http://links.lww.com/TXD/A352.

Distinctive waves of innate immune response in the retina in experimental autoimmune encephalomyelitis.

Neurodegeneration mediates neurological disability in inflammatory demyelinating diseases of the CNS. The role of innate immune cells in mediating this damage has remained controversial with evidence for destructive and protective effects. This has complicated efforts to develop treatment. The time sequence and dynamic evolution of the opposing functions are especially unclear. Given limits of in vivo monitoring in human diseases such as multiple sclerosis (MS), animal models are warranted to investigate the association and timing of innate immune activation with neurodegeneration. Using noninvasive in vivo retinal imaging of experimental autoimmune encephalitis (EAE) in CX3CR1GFP/+-knock-in mice followed by transcriptional profiling, we are able to show 2 distinct waves separated by a marked reduction in the number of innate immune cells and change in cell morphology. The first wave is characterized by an inflammatory phagocytic phenotype preceding the onset of EAE, whereas the second wave is characterized by a regulatory, antiinflammatory phenotype during the chronic stage. Additionally, the magnitude of the first wave is associated with neuronal loss. Two transcripts identified - growth arrest-specific protein 6 (GAS6) and suppressor of cytokine signaling 3 (SOCS3) - might be promising targets for enhancing protective effects of microglia in the chronic phase after initial injury.