Glu592 of the axon guidance receptor ROBO3 mediates a pH-dependent interaction with NELL2 ligand.

There are only a few studies on the function of neuronal axon guidance molecules during low brain pH conditions. We previously reported that roundabout (ROBO) 2, a receptor for the axon guidance molecule SLIT, can bind to the neural epidermal growth factor-like-like (NELL) ligands in acidic conditions by conformational change of its ectodomain. Here, we show that the ROBO3 receptor also exhibits a pH-dependent increase in binding to the NELL2 ligand.

Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis.

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community.

Mammalian neurotoxins, Blarina paralytic peptides, cause hyperpolarization of human T-type Ca channel hCa3.2 activation.

Among the rare venomous mammals, the short-tailed shrew Blarina brevicauda has been suggested to produce potent neurotoxins in its saliva to effectively capture prey. Several kallikrein-like lethal proteases have been identified, but the active substances of B. brevicauda remained unclear.

ALPL-1 is a target for chimeric antigen receptor therapy in osteosarcoma.

Osteosarcoma (OS) remains a dismal malignancy in children and young adults, with poor outcome for metastatic and recurrent disease. Immunotherapies in OS are not as promising as in some other cancer types due to intra-tumor heterogeneity and considerable off-target expression of the potentially targetable proteins. Here we show that chimeric antigen receptor (CAR) T cells could successfully target an isoform of alkaline phosphatase, ALPL-1, which is highly and specifically expressed in primary and metastatic OS.

Our Voice in a rural community: empowering Colombian adolescents to advocate for school community well-being through citizen science.

Background: Santa Ana is home to an Afro-descendant rural population of the island of Barú in Cartagena, Colombia. While a popular area for tourism, Santa Ana's population is affected by multidimensional poverty, precarious work conditions, homelessness, broken streets and sewer systems, limited quality education, and a lack of recreation and sport spaces. While Santa Ana's Community Action Board aims to unify efforts and resources to solve these problems, the state's capacity to meet the requirements of the Board is limited.

Conformational Change of the Hairpin-like-structured Robo2 Ectodomain Allows NELL1/2 Binding.

Since neural epidermal growth factor-like-like (NELL) 2 was identified as a novel ligand for the roundabout (Robo) 3 receptor, research on NELL-Robo signaling has become increasingly important. We have previously reported that Robo2 can bind to NELL1/2 in acidic conditions but not at neutral pH. The NELL1/2-binding site that is occluded in neutral conditions is thought to be exposed by a conformational change of the Robo2 ectodomain upon exposure to acidic pH; however, the underlying structural mechanisms are not well understood.

Cryo-EM structures of thylakoid-located voltage-dependent chloride channel VCCN1.

In the light reaction of plant photosynthesis, modulation of electron transport chain reactions is important to maintain the efficiency of photosynthesis under a broad range of light intensities. VCCN1 was recently identified as a voltage-gated chloride channel residing in the thylakoid membrane, where it plays a key role in photoreaction tuning to avoid the generation of reactive oxygen species (ROS). Here, we present the cryo-EM structures of Malus domestica VCCN1 (MdVCCN1) in nanodiscs and detergent at 2.

Advanced catalytic oxidation coupled to biological systems to treat pesticide-contaminated water: A review on technological trends and future challenges.

This article had the one and only objective of consolidating the couplings of advanced oxidation processes and biological systems in the decontamination of wastewater with pesticide content reported in the Scopus and Web of Science databases, through a critical analysis of which have been the most used, what methodologies have been implemented to develop them, identifying the objectives of each work, determining the success of the research and where the main niches of knowledge are, which can lead to the generation of new scientific knowledge as well as future trends. A co-occurrence analysis was carried out through the VOSViewer software to determine the most associated key words with the treatment configurations described above. Fenton and Photo-Fenton processes, heterogeneous photocatalysis TiO/UV, electrocatalysis, ozonization and a particular case of hydrodynamic cavitation-ozone as main advanced oxidation processes, together with advanced biological processes such as sequential batch bioreactor (SBR), membrane bioreactor (MBR), mobile bed biofilm reactor (MBBR); biodegradability and toxicity tests with bacterial strains and surface wetlands, whose treatment philosophy is activated sludge.

Predictive Validity of Developmental Screening Questionnaires for Identifying Children With Later Cognitive or Educational Difficulties: A Systematic Review.

Parent/caregiver completing developmental screening questionnaires (DSQs) for children before 5 years of age is currently recommended. The DSQs recommended by the American Academy of Pediatrics (AAP) are the Ages and Stages Questionnaires (ASQ), Parents' Evaluation of Developmental Status (PEDS), and the Survey of Well-being of Young Children (SWYC). Nevertheless, their predictive validity has not been well-established.

[Professionalism and self-care in residents, how should we confront their training?].

Professionalism is a well-defined competence in the education of residents. However, it is a complex construct, sensitive to social and cultural variables. It can be defined as the necessary skill, good jud gment and appropriate behavior expected of people trained to do their jobs well.

The structure of MgtE in the absence of magnesium provides new insights into channel gating.

MgtE is a Mg2+ channel conserved in organisms ranging from prokaryotes to eukaryotes, including humans, and plays an important role in Mg2+ homeostasis. The previously determined MgtE structures in the Mg2+-bound, closed-state, and structure-based functional analyses of MgtE revealed that the binding of Mg2+ ions to the MgtE cytoplasmic domain induces channel inactivation to maintain Mg2+ homeostasis. There are no structures of the transmembrane (TM) domain for MgtE in Mg2+-free conditions, and the pore-opening mechanism has thus remained unclear.

Id2 Represses Aldosterone-Stimulated Cardiac T-Type Calcium Channels Expression.

Aldosterone excess is a cardiovascular risk factor. Aldosterone can directly stimulate an electrical remodeling of cardiomyocytes leading to cardiac arrhythmia and hypertrophy. L-type and T-type voltage-gated calcium (Ca) channels expression are increased by aldosterone in cardiomyocytes.

Interactive Guidance Intervention to Address Sustained Social Withdrawal in Preterm Infants in Chile: Protocol for a Randomized Controlled Trial.

Background: Preterm newborns can be exposed early to significant perinatal stress, and this stress can increase the risk of altered socioemotional development. Sustained social withdrawal in infants is an early indicator of emotional distress which is expressed by low reactivity to the environment, and if persistent, is frequently associated with altered psychological development. Infants born prematurely have a higher probability of developing sustained social withdrawal (adjusted odds ratio 1.

Association of Cow's Milk Protein Allergy Prevalence With Socioeconomic Status in a Cohort of Chilean Infants.

Objectives: The aim of the study was to compare the cow's milk protein allergy (CMPA) prevalence in 2 cohorts of children from different socioeconomic strata.

Methods: Prospective birth cohort that included patients from 2 hospitals providing care for a low- and high-income population, respectively. Healthy newborns ≥34 gestational weeks were recruited and followed up to 12 months by a monthly telephone survey.

Assessment of the NO distribution and relationship with traffic load in the Caribbean coastal city.

NO ambient concentrations were measured in a coastal Caribbean city. Barranquilla is a Caribbean city located in the North of Colombia that has approximately 1.200.

Systematic Reviews in Neonatal Respiratory Care: Are Some Conclusions Misleading?

An increasing amount of information is currently available in neonatal respiratory care. Systematic reviews are an important tool for clinical decision-making. The challenge is to combine studies that address a specific clinical question and have similar characteristics in terms of populations, interventions, comparators, and outcomes, so that their combined results provide a more precise estimate of the effect that can be validly extrapolated into clinical practice.

Author Correction: Structural basis for the drug extrusion mechanism by a MATE multidrug transporter.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Randomized controlled trial comparing mini-sling with transobturator sling for the treatment of stress urinary incontinence.

Introduction And Hypothesis: Stress urinary incontinence (SUI) is the involuntary loss of urine on effort and is a condition that negatively interferes with various aspects of a woman's life. This study aimed to demonstrate the non-inferiority of the less invasive single-incision mini-sling (SIMS) method in objective and subjective cures in relation to tension-free transobturator tape (TOT) in two analyses, per protocol and intention to treat, and secondarily to evaluate complications and quality of life.

Methods: This study was a randomized controlled trial (RCT).

Comparison between Ages & Stages Questionnaire and Bayley Scales, to predict cognitive delay in school age.

Objective: To compare the predictive value of the Spanish Ages & Stages Questionnaire third edition adapted for Chilean population (ASQ-Cl) and the Bayley Scale of Infant and Toddler Development 3rd edition (Bayley-III) for cognitive delay at school age, and to identify the domain predictors.

Methodology: Data were collected from 306 term and preterm children of medium-high socio-economic level enrolled in a prospective cohort study. Developmental outcomes at 8, 18 and 30 months were assessed via the ASQ-Cl and Bayley-III; at 6-8 years cognitive development was assessed using the Wechsler Intelligence Scale for Children (WISC-III).

RBM20 Regulates CaV1.2 Surface Expression by Promoting Exon 9* Inclusion of in Neonatal Rat Cardiomyocytes.

The gene encodes for the CaV1.2 protein, which is the pore subunit of cardiac l-type voltage-gated calcium (Ca) channels (l-channels). Through alternative splicing, encodes for various CaV1.

Nuclear localization of β-catenin and expression of target genes are associated with increased Wnt secretion in oral dysplasia.

Objectives: To evaluate the localization of β-catenin in oral dysplastic cells, the expression of target genes upregulated in oral dysplasia, and the role of Wnt ligands in these events.

Materials And Methods: Subcellular localization of total and non-phosphorylated (transcriptionally active) β-catenin was evaluated by immunofluorescence and biochemical fractionation in dysplastic oral keratinocytes (DOK), non-dysplastic oral keratinocytes (OKF6), oral squamous carcinoma cells (CAL27) and primary oral keratinocytes. Tcf/Lef-dependent transcription was measured by luciferase reporter assays.

Robo2 contains a cryptic binding site for neural EGFL-like (NELL) protein 1/2.

The signaling pathways that are mediated by Slit ligands and their Roundabout (Robo) family of receptors play multifunctional roles in the development of the nervous system and other organs. A recent study identified neural epidermal growth factor-like (NEL)-like 2 (NELL2) as a novel ligand for Robo3. In this study, we carried out a comprehensive analysis of the interaction between NELL1 and the Robo family of receptors and demonstrated that Robo2 contains a cryptic binding site for both NELL1 and NELL2.