Sitetack: A Deep Learning Model that Improves PTM Prediction by Using Known PTMs.

Post-translational modifications (PTMs) increase the diversity of the proteome and are vital to organismal life and therapeutic strategies. Deep learning has been used to predict PTM locations. Still, limitations in datasets and their analyses compromise success. Here we evaluate the use of known PTM sites in prediction via sequence-based deep learning algorithms. Specifically, PTM locations were encoded as a separate amino acid before sequences were encoded via word embedding and passed into a convolutional neural network that predicts the probability of a modification at a given site. Without labeling known PTMs, our model is on par with others. With labeling, however, we improved significantly upon extant models. Moreover, knowing PTM locations can increase the predictability of a different PTM. Our findings highlight the importance of PTMs for the installation of additional PTMs. We anticipate that including known PTM locations will enhance the performance of other proteomic machine learning algorithms.

Association between preterm infant body composition in the first 3 months of life and preschool age: a cohort study.

Compared with full-term infants, preterm infants have fat-free mass deficit in the first months of life, which increases the risk of metabolic diseases in the future. In this cohort of children born under 32-week gestational age or less than 1500 g, we aimed to evaluate the associations of body composition at term equivalent age and in the first 3 months of life with fat-free mass and fat mass percentage at 4 to 7 years of life. Body composition assessments by air displacement plethysmography and anthropometry were performed at term, at 3 months of corrected age, and at 4 to 7 years of age. Multiple linear regression analysis was used to observe the associations between body composition at these ages. At term, fat mass percentage showed a negative association and fat-free mass a positive association with fat-free mass at 4 to 7 years. The fat-free mass at 3 months and the gain in fat-free mass between term and 3 months showed positive associations with fat-free mass at 4 to 7 years.   Conclusion: Body composition at preschool age is associated with fat-free mass in the first 3 months of life, a sensitive period for the risk of metabolic diseases. What is Known: • Preterm infants have a deficit in fat-free mass and high adiposity at term equivalent age compared to full-term infants. • Fat-free mass reflects metabolic capacity throughout life and therefore is considered a protective factor against the risk of metabolic syndrome. What is New: •Fat-free mass gain in the first 3 months of corrected age is associated with fat-free mass at preschool and school ages. •The first 3 months of life is a sensitive period to the risk of metabolic diseases.

Wildfire and cattle legacies on gradients of soil nitrogen underlie patterns of annual brome invasion.

Human activities are increasing wildfires and livestock activity in arid ecosystems with potential implications for the spread of invasive grasses. The objective of this study was to test whether fire history and cattle activity alter soil resource gradients, thereby affecting patterns of Bromus rubens L. (red brome) invasion. Six paired burned and unburned transect lines (1-km long) were established in the northeast Mojave Desert along the boundaries of four independent wildfire scars. At 100-m transect increment points, we measured the distance to the two nearest cowpats, and two random points and measured the density, height, biomass, and seed production of red brome, soil moisture and inorganic nitrogen (N). Cattle activity was 29% greater along burned transects compared to unburned transects (P < 0.05). Red brome height, density, and seed production were 11-34% greater along burned transects than unburned transects (P < 0.05). Red brome height, biomass, density, and seed production were twofold to tenfold greater next to cowpats compared to random points (P < 0.05). Soils along burned transects and beneath cowpats had greater soil inorganic N (P < 0.05), which was positively correlated with red brome density, height, biomass, and seed production (R2 = 0.60-0.85, P < 0.0001). Transgenerational effects were evident as seeds from red brome next to cowpats had 27% higher germination than seeds collected from random points. Positive responses of red brome to increased inorganic N related to fire and cattle activity may contribute fine fuel infill that drives invasive grass-fire cycles in deserts.

High-risk children and social isolation: the importance of family functioning.

High-risk newborns are exposed to neonatal conditions such as prematurity, very low birth weight, and congenital malformations that can affect development and behavior. Coronavirus disease 2019 (COVID-19) restraint and control measures have been identified as important stressor events and cumulative risk factors for behavioral changes in these children. This study examined social isolation-related factors that contribute to internalizing and externalizing behavior problems in children already at risk for neurodevelopmental disorders. This cross-sectional, multicenter study included 113 children (18 months to 9 years) who were followed in reference services for neonatal follow-up in tertiary units of the public health system in the city of Rio de Janeiro, Brazil. Behavior was assessed using the child behavior checklist, and a structured questionnaire was used to assess sociodemographic aspects. In the bivariate analysis, prematurity was associated with externalizing problems and change in eating habits with internalizing problems. The logistic model indicated that both parents having completed high school and both sharing care of the child were protective factors for behavioral problems; however, reports of sleep problems and living with another child were risk factors. In conclusion, the study identified internalizing and externalizing behavior problems related to prematurity and aspects of family structure and routine in children at risk. The findings confirm the importance of family functioning for child health and family-centered interventions.

Physical and social activities constraint and its effects on Body Mass Index of former Neonatal Intensive Care children.

OBJECTIVE: It is reported weight gain in children due to the confinement measures during the Covid-19 pandemic. We aimed to describe the effect of these measures on the nutritional status of former Neonatal Intensive Care Unit children. METHODS: Cross-sectional study, including former Neonatal Intensive Care Unit children. The outcome was the Body mass index (BMI). RESULTS: We enrolled 126 children (74.6 % preterm; 31 % small-for-gestational-age). Weight excess was greater in the youngest group (≤5 years: 33.8 %; >5 years: 15.2 %). Prematurity was associated with weight excess in both groups (≤5 years: p value 0.006; >5 years: p value 0.046; Pearson test). Mealtime changes, lack of physical activity, socioeconomic factors and the perinatal morbidities significantly influenced the mean BMI. Birth length Z score less than -1.28 was negatively associated with BMI, while gestational age at birth presented a positive association with BMI (linear regression model). CONCLUSIONS: The BMI increase due to the confinement measures associated with the gestational age at birth and in those born with intrauterine growth restriction is a matter of concern, as it might indicate a risk for future obesity.

Chemoselective Caging of Carboxyl Groups for On-Demand Protein Activation with Small Molecules.

Tools for on-demand protein activation enable impactful gain-of-function studies in biological settings. Thus far, however, proteins have been chemically caged at primarily Lys, Tyr, and Sec, typically through the genetic encoding of unnatural amino acids. Herein, we report that the preferential reactivity of diazo compounds with protonated acids can be used to expand this toolbox to solvent-accessible carboxyl groups with an elevated pKa value. As a model protein, we employed lysozyme (Lyz), which has an active-site Glu35 residue with a pKa value of 6.2. A diazo compound with a bioorthogonal self-immolative handle esterified Glu35 selectively, inactivating Lyz. The hydrolytic activity of the caged Lyz on bacterial cell walls was restored with two small-molecule triggers. The decaging was more efficient by small molecules than by esterases. This simple chemical strategy was also applied to a hemeprotein and an aspartyl protease, setting the stage for broad applicability.

Early growth and body composition assessed by air displacement plethysmography in infants born with simple gastroschisis.

BACKGROUND: Gastroschisis is an abdominal wall malformation usually associated with impaired growth. OBJECTIVE: To evaluate the growth and body composition of infants born with simple gastroschisis in a referral center. METHODS: This was a single-center, prospective case series of infants with simple gastroschisis who were measured at birth, at discharge, and at 3 months. Body composition was assessed via air-displacement plethysmography at discharge and at 3 months. The results were compared with those reported for healthy infants at an equivalent gestational age. RESULTS: Simple gastroschisis infants were lighter and smaller at birth and remained similar at 3 months. All anthropometric z scores decreased from birth to discharge, followed by an increase but not a full recovery toward 3 months. Overall, gastroschisis infants had a similar FM percentage, FM% (11.1 ± 4.7), but a lower FFM, FFM (2481 ± 478 g), at discharge. FM% (18.5 ± 5.3) decreased at 3 months, and FFM remained lower (3788 ± 722 g) but improved between the two exams. Boys had significantly more FFM than girls at both evaluations. The multiple regression analysis showed that male sex, prematurity, total parenteral nutrition duration, and exclusive breast milk diets were associated with differences in body composition. CONCLUSIONS: Infants with simple gastroschisis cared for in a referral center experienced growth failure at discharge and showed a similar FM% but lower FFM than healthy infants. At 3 months, they exhibited smaller FM% and FFM, but FFM improved after the first exam, representing a better protein accretion. TYPE OF STUDY: Prognostic. LEVEL OF EVIDENCE: IV.

Resting energy expenditure in preterm newborns with bronchopulmonary dysplasia.

BACKGROUND & AIMS: Greater energy expenditure is reported in newborns with bronchopulmonary dysplasia (BPD). This study assessed resting energy expenditure (REE) in newborns with BPD. METHODS: BPD was classified as mild and moderate/severe. REE was assessed using indirect calorimetry between the time points of the discontinuation of oxygen (O2) (T1) and at term-equivalent age (T2) in preterm newborns with BPD. RESULTS: The moderate group (10 newborns) presented with higher REE (kcal/kg/day) after discontinuation of mechanical ventilation and a decrease of 18% between the two time points; 72.7 and 59.6 kcal/kg/day at T1 and T2 respectively (p value 0.08). No differences were observed in REE in the mild BPD group between timepoints; 50.9-56.4 kcal/kg/day at T1 and T2 respectively (p value 0.73). CONCLUSION: Newborns with BPD presented different metabolic behaviors depending on the classification criteria: those classified as having moderate BPD showed a decrease in REE toward term-equivalent age.

Energy expenditure and body composition in infants with bronchopulmonary dysplasia at term age.

In this cross-sectional study, conducted in a cohort of infants with a gestational age of < 32 weeks, we aimed to evaluate and compare resting energy expenditure (REE) and body composition between infants who developed bronchopulmonary dysplasia (BPD) and those who did not. REE and body composition were assessed at term equivalent age using indirect calorimetry and air displacement plethysmography. Anthropometric measurements (weight, head circumference, and length) were obtained and transformed into Z-scores per the Fenton (2013) growth curve, at birth and at term equivalent age. Forty-two infants were included in this study, of which 26.2% developed BPD. Infants with BPD had significantly higher energy expenditure at term equivalent age, with no difference in body composition between the two groups. CONCLUSION: Despite expending more energy, infants with BPD maintained a similar body composition distribution to those without BPD, and this is likely due to the recommended nutritional approach. WHAT IS KNOWN: • Greater resting energy expenditure impairs growth of preterm infants with bronchopulmonary dysplasia. WHAT IS NEW: • Although preterm infants with bronchopulmonary dysplasia had a higher resting energy expenditure at the corrected term age, this did not affect their body composition and growth.

[Know-how and techniques of Family Health Strategy managers and professionals in the prevention of violence against adolescents]. / Conhecimentos e práticas de gerentes e profissionais da ESF na prevenção das violências com adolescentes.

The scope of this study was to identify empowering factors for the actions of the Family Health Strategy (FHS) in coping with violence among adolescents. The sample was random from 61 teams of the Family Health Strategy of three municipalities. Questionnaires tabulated by EpiINFO 7.0, with bivariate analyses were used. Chi-square, Fisher and the "classification tree" were then used to analyze the experiences in this theme and the following issues: bonding, time since training completed, qualification, knowledge of public policies among others. There is acknowledgement of adolescents' vulnerability to violence, however, only two teams have ongoing prevention experiences. The prevailing opinion is that such activities are not the responsibility of the FHS. The study identifies interdependent variables that increase the likelihood of preventing violence and the promoting of a culture of peace among adolescents.

Este estudo objetivou identificar fatores potencializadores das ações da Estratégia Saúde da Família (ESF) no enfrentamento das violências contra adolescentes. A amostra foi aleatória de 61 equipes da ESF de três municípios. Utilizou-se questionários tabulados pelo programa EpiINFO 7.0, com análises bivariadas: qui-quadrado, Fisher e "árvore de classificação", para análise das experiências nessa temática e das seguintes questões - vínculo, tempo de formado, capacitação, conhecimento de políticas públicas, entre outras. Há o reconhecimento da vulnerabilidade dos adolescentes às violências, porém apenas duas equipes possuem experiências de prevenção com continuidade. Predomina a opinião de que tais atividades não competem à ESF. O estudo identifica variáveis interdependentes que aumentam a probabilidade da prevenção das violências e a promoção de cultura de paz entre adolescentes.

Conhecimentos e práticas de gerentes e profissionais da ESF na prevenção das violências com adolescentes / Know-how and techniques of Family Health Strategy managers and professionals in the prevention of violence against adolescents

Resumo Este estudo objetivou identificar fatores potencializadores das ações da Estratégia Saúde da Família (ESF) no enfrentamento das violências contra adolescentes. A amostra foi aleatória de 61 equipes da ESF de três municípios. Utilizou-se questionários tabulados pelo programa EpiINFO 7.0, com análises bivariadas: qui-quadrado, Fisher e "árvore de classificação", para análise das experiências nessa temática e das seguintes questões - vínculo, tempo de formado, capacitação, conhecimento de políticas públicas, entre outras. Há o reconhecimento da vulnerabilidade dos adolescentes às violências, porém apenas duas equipes possuem experiências de prevenção com continuidade. Predomina a opinião de que tais atividades não competem à ESF. O estudo identifica variáveis interdependentes que aumentam a probabilidade da prevenção das violências e a promoção de cultura de paz entre adolescentes.

Abstract The scope of this study was to identify empowering factors for the actions of the Family Health Strategy (FHS) in coping with violence among adolescents. The sample was random from 61 teams of the Family Health Strategy of three municipalities. Questionnaires tabulated by EpiINFO 7.0, with bivariate analyses were used. Chi-square, Fisher and the "classification tree" were then used to analyze the experiences in this theme and the following issues: bonding, time since training completed, qualification, knowledge of public policies among others. There is acknowledgement of adolescents' vulnerability to violence, however, only two teams have ongoing prevention experiences. The prevailing opinion is that such activities are not the responsibility of the FHS. The study identifies interdependent variables that increase the likelihood of preventing violence and the promoting of a culture of peace among adolescents.

Megafire affects stream sediment flux and dissolved organic matter reactivity, but land use dominates nutrient dynamics in semiarid watersheds.

Climate change is causing larger wildfires and more extreme precipitation events in many regions. As these ecological disturbances increasingly coincide, they alter lateral fluxes of sediment, organic matter, and nutrients. Here, we report the stream chemistry response of watersheds in a semiarid region of Utah (USA) that were affected by a megafire followed by an extreme precipitation event in October 2018. We analyzed daily to hourly water samples at 10 stream locations from before the storm event until three weeks after its conclusion for suspended sediment, solute and nutrient concentrations, water isotopes, and dissolved organic matter concentration, optical properties, and reactivity. The megafire caused a ~2,000-fold increase in sediment flux and a ~6,000-fold increase in particulate carbon and nitrogen flux over the course of the storm. Unexpectedly, dissolved organic carbon (DOC) concentration was 2.1-fold higher in burned watersheds, despite the decreased organic matter from the fire. DOC from burned watersheds was 1.3-fold more biodegradable and 2.0-fold more photodegradable than in unburned watersheds based on 28-day dark and light incubations. Regardless of burn status, nutrient concentrations were higher in watersheds with greater urban and agricultural land use. Likewise, human land use had a greater effect than megafire on apparent hydrological residence time, with rapid stormwater signals in urban and agricultural areas but a gradual stormwater pulse in areas without direct human influence. These findings highlight how megafires and intense rainfall increase short-term particulate flux and alter organic matter concentration and characteristics. However, in contrast with previous research, which has largely focused on burned-unburned comparisons in pristine watersheds, we found that direct human influence exerted a primary control on nutrient status. Reducing anthropogenic nutrient sources could therefore increase socioecological resilience of surface water networks to changing wildfire regimes.

Assessment of early nutritional intake in preterm infants with bronchopulmonary dysplasia: a cohort study.

This cohort study evaluated the nutritional supply in 78 very preterm newborns, with 20.5% developing bronchopulmonary dysplasia (BPD). This work aimed to evaluate the nutritional intake and the calorie/protein ratio received in the first 4 weeks of life. Anthropometric measures at birth and term age, the weight at each of the first 4 weeks of life, and the feeding practices were registered. The mean gestational age and birth weight were lower in those who developed BPD. At term age, head circumference and length Z-scores were significantly lower in newborns with BPD, who started enteral feeding and reached full diet later, staying longer in parenteral nutrition. The protein rate received by all newborns was similar, whether developing BPD or not, but those who developed BPD received significantly lower fluid volume and calorie rates after the second week. The daily calorie/protein ratio (30 kcal/1-g protein) was reached by 88.7% of the newborns who did not develop BPD in the third week, with those who developed BPD receiving less than this ratio until the second week, persisting in 56.3% of them on the fourth week.Conclusion: A calorie/protein ratio below that recommended for growth was found in preterm newborns who developed BPD, and providing nutrition for these newborns remains a challenge. What is Known: • The importance of preterm newborn nutrition is well known. • Early nutritional support may avoid severe BPD. What is New: • Newborns who developed BPD received a calorie/protein ratio below that recommended for preterm newborns' growth during the first 2 weeks of life, lasting until the fourth week in most of these newborns.

Predictive factors for sepsis by carbapenem resistant Gram-negative bacilli in adult critical patients in Rio de Janeiro: a case-case-control design in a prospective cohort study.

BACKGROUND: Studies have investigated risk factors for infections by specific species of carbapenem-resistant Gram-negative bacilli (CR-GNB), but few considered the group of GNB species and most of them were performed in the setting of bacteremia or hospital infection. This study was implemented to identify risk factors for sepsis by CR- and carbapenem-susceptible (CS) GNB in intensive care unit (ICU) patients to improve management strategies for CR-GNB sepsis. METHODS: We developed a case-case-control study from a prospective cohort of patients with systemic inflammatory response syndrome (SIRS), sepsis-2 or sepsis-3 criteria in which blood and other sample cultures were collected and antimicrobial therapy was instituted, in an adult clinical-surgical ICU, at tertiary public hospital in Rio de Janeiro, from August 2015 through March 2017. RESULTS: Among the total of 629 ICU admissions followed by 7797 patient-days, after applying inclusion and exclusion criteria we identified 184 patients who developed recurrent or single hospital-acquired sepsis. More than 90% of all evaluable cases of sepsis and 87% of control group fulfilled the modified sepsis-3 definition. Non-fermenting bacilli and ventilator-associated pneumonia predominated as etiology and source of CR-GNB sepsis. While Enterobacteriaceae and intra-abdominal surgical site plus urinary-tract infections prevailed in CS-GNB than CR-GNB sepsis. Carbapenemase production was estimated in 76% of CR-GNB isolates. Multivariate logistic regression analysis revealed previous infection (mostly hospital-acquired bacterial infection or sepsis) (OR = 4.28; 95% CI 1.77-10.35), mechanical ventilation (OR = 4.21; 95% CI 1.17-15.18), carbapenem use (OR = 3.42; 95% CI 1.37-8.52) and length of hospital stay (OR = 1.03; 95% CI 1.01-1.05) as independent risk factors for sepsis by CR-GNB. While ICU readmission (OR = 6.92; 95% CI 1.72-27.78) and nosocomial diarrhea (OR = 5.32; 95% CI 1.07-26.45) were factors associated with CS-GNB sepsis. CONCLUSIONS: The investigation of recurrent and not only bacteremic episodes of sepsis was the differential of this study. The results are in agreement with the basic information in the literature. This may help improve management strategies and future studies on sepsis by CR-GNB.

Predictors for de novo stress urinary incontinence following pelvic reconstructive surgery with mesh.

OBJECTIVE: The aims of this study are to describe the postoperative incidence of de novo stress urinary incontinence (SUI) in women who underwent anterior vaginal compartment prolapse repair using synthetic polypropylene mesh and to identify risk factors for this outcome. STUDY DESIGN: A retrospective cohort study of 146 women who underwent anterior vaginal repair from 2007 to 2017 and followed by a minimum period of 12 months was performed. The incidence of de novo SUI was evaluated at 3 and 12 months of follow-up. Women with concomitant or prior anti-incontinence surgery were not included. Preoperatively, all patients had a negative stress test and no evidence of occult SUI on urodynamics. The outcome was considered positive if the patient had complaints of SUI at the follow-up. Variables associated with the outcome with a p-value ≤ 0.10 were included in a logistic regression model to calculate the relative risk (RR) for de novo SUI. For multivariate analysis, all analyzes were performed considering a significant p-value ≤ 0.05. RESULTS: The incidence of de novo SUI at 3 and 12 months of follow-up was 15.8 % and 20.5 %, respectively. Higher body mass index (BMI), diabetes, anterior vaginal wall prolapse stage ≥ 3, older age at first pregnancy and higher first desire to void during the urodynamic evaluation were positively associated with de novo SUI in the bivariate analysis (p ≤ 0.10). Previous perineoplasty had a negative association with the outcome analyzed, suggesting a protective effect. After the multivariate analysis, higher BMI (RR 1.19, 95 % confidence interval [CI] 1.05-1.36), diabetes (RR 4.18, 95 % CI 1.32-13.21) and anterior vaginal wall prolapse stage ≥ 3 (RR 14.74, 95 % CI 1.64-132.0) remained as risk factors for de novo SUI (p ≤ 0.01). CONCLUSION: The incidence of de novo SUI after the surgical correction of anterior vaginal wall prolapse with synthetic mesh in this population was 15.8 % and 20.5 % at 3 and 12 months of follow-up, respectively. Continent women who underwent this surgical procedure and who had a higher BMI, diabetes and anterior vaginal wall prolapse stage ≥ 3 had a higher risk of presenting de novo SUI.

Forming Weakly Interacting Multilayers of Graphene Using Atomic Force Microscope Tip Scanning and Evidence of Competition between Inner and Outer Raman Scattering Processes Piloted by Structural Defects.

We report on an alternative route based on nanomechanical folding induced by an AFM tip to obtain weakly interacting multilayer graphene (wi-MLG) from a chemical vapor deposition (CVD)-grown single-layer graphene (SLG). The tip first cuts and then pushes and folds graphene during zigzag movements. The pushed graphene has been analyzed using various Raman microscopy plots- AD/ AG × EL4 vs ΓG, ω2D vs Γ2D, Γ2D vs ΓG, ω2D+/- vs Γ2D+/-, and A2D-/ A2D+ vs A2D/ AG. We show that the SLG in-plane properties are maintained under the folding process and that a few tens of graphene layers are stacked, with a limited number of structural defects. A blue shift of about 20 cm-1 of the 2D band is observed. The relative intensity of the 2D- and 2D+ bands have been related to structural defects, giving evidence of their role in the inner and outer processes at play close to the Dirac cone.

Growth and body composition in preterm newborns with bronchopulmonary dysplasia: a cohort study.

Objective To compare growth and body composition of preterm infants (gestational age <32 weeks) with and without bronchopulmonary dysplasia (BPD). Methods A prospective cohort involving three neonatal units in the public health system of the Brazilian city of Rio de Janeiro. Inclusion: newborns with gestational age <32 weeks. EXPOSURE: BPD. Anthropometric measurements were performed at birth and at 1 month of infant corrected age. Body composition was measured using an air displacement plethysmography (ADP) (PEA POD®) at 1 month of infant corrected age. Results Ninety-five newborns were eligible, of which 67 were included, 32.8% of them with BPD. Newborns with BPD presented lower gestational age at birth, greater need for resuscitation in the delivery room, received parenteral nutrition (PN) for a longer period of time, achieved lower weights during hospital stay and required more time to reach a full enteral diet. No statistically significant differences were observed in relation to anthropometric measurements and body composition at 1 month of infant corrected age between the groups with and without BPD. Conclusion This study, unlike previous ones, has shown that children who developed BPD were able to regain growth, as measured by anthropometric measures, with no change in body composition at 1 month of infant corrected age.

A matemática ajudando a entender o crescimento das crianças

Videoaula sobre "A matemática ajudando a entender o crescimento das crianças", por Saint Clair S. Gomes Junior, pesquisador da Fiocruz no Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF/Fiocruz), durante a Semana Nacional de Ciência e Tecnologia (SNCT) de 2017 com o tema "A Matemática está em tudo" e por meio da realização do Colóquio Fiocruz, os pesquisadores apresentaram como a matemática está na saúde.

Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase.

Upon different types of stress, the gene encoding the mitosis-promoting phosphatase Cdc25C is transcriptionally repressed by p53, contributing to p53's enforcement of a G2 cell cycle arrest. In addition, Cdc25C protein stability is also decreased following DNA damage. Mdm2, another p53 target gene, encodes a ubiquitin ligase that negatively regulates p53 levels by ubiquitination. Ablation of Mdm2 by siRNA led to an increase in p53 protein and repression of Cdc25C gene expression. However, Cdc25C protein levels were actually increased following Mdm2 depletion. Mdm2 is shown to negatively regulate Cdc25C protein levels by reducing its half-life independently of the presence of p53. Further, Mdm2 physically interacts with Cdc25C and promotes its degradation through the proteasome in a ubiquitin-independent manner. Either Mdm2 overexpression or Cdc25C downregulation delays cell cycle progression through the G2/M phase. Thus, the repression of the Cdc25C promoter by p53, together with p53-dependent induction of Mdm2 and subsequent degradation of Cdc25C, could provide a dual mechanism by which p53 can enforce and maintain a G2/M cell cycle arrest.