Vitamin B6 is governed by the local compartmentalization of metabolic enzymes during growth.

Vitamin B6 is a vital micronutrient across cell types and tissues, and dysregulated B6 levels contribute to human disease. Despite its importance, how B6 vitamer levels are regulated is not well understood. Here, we provide evidence that B6 dynamics are rapidly tuned by precise compartmentation of pyridoxal kinase (PDXK), the rate-limiting B6 enzyme. We show that canonical Wnt rapidly led to the accumulation of inactive B6 by shunting cytosolic PDXK into lysosomes. PDXK was modified with methyl-arginine Degron (MrDegron), a protein tag for lysosomes, which enabled delivery via microautophagy. Hyperactive lysosomes resulted in the continuous degradation of PDXK and B6 deficiency that promoted proliferation in Wnt-driven colorectal cancer (CRC) cells. Pharmacological or genetic disruption of the coordinated MrDegron proteolytic pathway was sufficient to reduce CRC survival in cells and organoid models. In sum, this work contributes to the repertoire of micronutrient-regulated processes that enable cancer cell growth and provides insight into the functional impact of B6 deficiencies for survival.

Hitting the Sweet Spot: How Glucose Metabolism Is Orchestrated in Space and Time by Phosphofructokinase-1.

Glycolysis is the central metabolic pathway across all kingdoms of life. Intensive research efforts have been devoted to understanding the tightly orchestrated processes of converting glucose into energy in health and disease. Our review highlights the advances in knowledge of how metabolic and gene networks are integrated through the precise spatiotemporal compartmentalization of rate-limiting enzymes. We provide an overview of technically innovative approaches that have been applied to study phosphofructokinase-1 (PFK1), which represents the fate-determining step of oxidative glucose metabolism. Specifically, we discuss fast-acting chemical biology and optogenetic tools that have delineated new links between metabolite fluxes and transcriptional reprogramming, which operate together to enact tissue-specific processes. Finally, we discuss how recent paradigm-shifting insights into the fundamental basis of glycolytic regulatory control have shed light on the mechanisms of tumorigenesis and could provide insight into new therapeutic vulnerabilities in cancer.

Ease of Handling and Physiological Parameters of Stress, Carcasses, and Pork Quality of Pigs Handled in Different Group Sizes.

The effect of different group sizes of pigs (3, 5, and 10 pigs) during handling on physiological parameters, carcasses, and pork quality traits at the farm and slaughterhouse were evaluated in 360 pigs from five farms (four repetitions or group/treatment/farms). Data was analyzed as a factorial of 3 × 5 (3 treatments × 5 farms) to check effects of treatments by analysis of variance in ANOVA. Ease of handling decreased as the group size increased. However, time taken in handling was not influenced by the group size (p > 0.10). Moving pigs in groups of five animals reduced effects on blood cortisol levels (p < 0.05). Fighting and handling lesions in the carcasses increased for bigger handling groups (p < 0.05). Pigs handled in groups of three and ten animals had a higher pHu and initial temperature in Longissimus thoracis and Semimembranosus (p < 0.05) and lower drip loss in Semimembranosus (p < 0.05). However, meat quality classifications of the carcasses were not affected by treatments. Based on the results, moving groups of five pigs seems to be the best strategy to improve animal welfare, carcasses and pork quality.

An attentional bias for LEGO® people using a change detection task: Are LEGO® people animate?

Animate objects have been shown to elicit attentional priority in a change detection task. This benefit has been seen for both human and nonhuman animals compared with inanimate objects. One explanation for these results has been based on the importance animate objects have served over the course of our species' history. In the present set of experiments, we present stimuli, which could be perceived as animate, but with which our distant ancestors would have had no experience, and natural selection could have no direct pressure on their prioritization. In the first experiment, we compared LEGO® "people" with LEGO "nonpeople" in a change detection task. In a second experiment, we attempt to control the heterogeneity of the nonanimate objects by using LEGO blocks, matched in size and colour to LEGO people. In the third experiment, we occlude the faces of the LEGO people to control for facial pattern recognition. In the final 2 experiments, we attempt to obscure high-level categorical information processing of the stimuli by inverting and blurring the scenes. (PsycINFO Database Record

Linfoma Malt primário de corpo uterino: relato de caso / Primary lymphoma of the uterine corpus: case report

Linfoma MALT dificilmente acometem o trato gênito-urinário, manifestando-se preferencialmente em vagina e ovários, sendo o útero raramente comprometido. Nossa paciente é uma mulher, 50 anos, portadora do vírus da imunodeficiência humana, com menopausa há um ano, que procurou assistência médica após apresentar sangramento uterino. O ultra-som transvaginal, verificou espessamento endometrial. Foi submetida à curetagem uterina e em seguida a uma histerectomia total, pela hipótese de câncer endometrial. A patologia demonstrou tratar-se de Linfoma Não-Hodgkin e a imuno-histoquímica foi compatível com o subtipo MALT. Foi submetida à quimioterapia complementar, sem sinais de recidiva da doença até o momento (AU)

Linfoma Malt primário de corpo uterino: relato de caso

Linfoma MALT dificilmente acometem o trato gênito-urinário, manifestando-se preferencialmente em vagina e ovários, sendo o útero raramente comprometido. Nossa paciente é uma mulher, 50 anos, portadora do vírus da imunodeficiência humana, com menopausa há um ano, que procurou assistência médica após apresentar sangramento uterino. O ultra-som transvaginal, verificou espessamento endometrial. Foi submetida à curetagem uterina e em seguida a uma histerectomia total, pela hipótese de câncer endometrial. A patologia demonstrou tratar-se de Linfoma Não-Hodgkin e a imuno-histoquímica foi compatível com o subtipo MALT. Foi submetida à quimioterapia complementar, sem sinais de recidiva da doença até o momento

Estimativa de correlações entre medidas morfométricas, peso do ovo e peso de filhotes de emas criados em cativeiro / Correlations estimate among morfometrics measures, eggs weight and rhea chicls weight raised in captivity

Foram coletados 68 ovos de Ema no período de 8 de agosto a 13 de setembro de 2003, em Quirinópolis, Goiás, Brasil. O objetivo foi avaliar a correlação entre peso do ovo (PO), características morfométricas: comprimento do ovo (CO), largura do ovo (LO), circunferência do ovo (CIO), comprimento da câmara de ar (CCA), espessura da casca (EC); peso ao nascimento (PN) e equivalência de peso (EP). O peso do ovo teve correlação significativa (P < 0,01) com CO, LO e CIO; CO apresentou correlação significativa (P < 0,05) com LO e CIO; LO foi correlacionada significativamente (P < 0,01) com CIO e (P < 0,05) CCA; a CIO teve correlação significativa (P > 0,05) com CCA; CCA teve correlação significativa (P < 0,01) com EC; a EC apresentou correlação significativa (P < 0,01) com PN e PN teve correlação significativa (P < 0,01) com EP. Observou-se que o peso do ovo não constitui característica de seleção e o comprimento da câmara de ar (CCA) foi a variável considerada ideal para seleção de embriões viáveis aos quinze dias de incubação, quando são comercializados fertilizados.