Infants' Social Evaluation of Helpers and Hinderers: A Large-Scale, Multi-Lab, Coordinated Replication Study.

Evaluating whether someone's behavior is praiseworthy or blameworthy is a fundamental human trait. A seminal study by Hamlin and colleagues in 2007 suggested that the ability to form social evaluations based on third-party interactions emerges within the first year of life: infants preferred a character who helped, over hindered, another who tried but failed to climb a hill. This sparked a new line of inquiry into the origins of social evaluations; however, replication attempts have yielded mixed results.

How to build up big team science: a practical guide for large-scale collaborations.

The past decade has witnessed a proliferation of big team science (BTS), endeavours where a comparatively large number of researchers pool their intellectual and/or material resources in pursuit of a common goal. Despite this burgeoning interest, there exists little guidance on how to create, manage and participate in these collaborations. In this paper, we integrate insights from a multi-disciplinary set of BTS initiatives to provide a how-to guide for BTS.

Claudin-4 localization in epithelial ovarian cancer.

Claudin-4, a protein with the structure of classic claudins most often found in cell-cell junctions, is frequently overexpressed in epithelial cancers where its localization has not been studied. In this study we aimed to find out where this membrane protein is localized in an ovarian tumor model, OVCAR3 cells, that express high levels of the protein. Immunohistochemical studies showed claudin-4 staining in a perinuclear region, at most plasma membranes and in cytoplasmic puncta.

Loss of Claudin-4 Reduces DNA Damage Repair and Increases Sensitivity to PARP Inhibitors.

High-grade serous ovarian cancer is the deadliest gynecologic malignancy due to progression to resistant disease. Claudin-4 is classically defined as a tight junction protein and is often associated with epithelial cancers. Claudin-4 is aberrantly expressed in nearly 70% of all ovarian cancer tumors and conveys a worse overall prognosis.

Ovarian Tumor Cell Expression of Claudin-4 Reduces Apoptotic Response to Paclitaxel.

A significant factor contributing to poor survival rates for patients with ovarian cancer is the insensitivity of tumors to standard-of-care chemotherapy. In this study, we investigated the effect of claudin-4 expression on ovarian tumor cell apoptotic response to cisplatin and paclitaxel. We manipulated claudin-4 gene expression by silencing expression [short hairpin RNA (shRNA)] in cells with endogenously expressed claudin-4 or overexpressing claudin-4 in cells that natively do not express claudin-4.

The origins of cortical multisensory dynamics: Evidence from human infants.

Classic views of multisensory processing suggest that cortical sensory regions are specialized. More recent views argue that cortical sensory regions are inherently multisensory. To date, there are no published neuroimaging data that directly test these claims in infancy.

An eye tracking investigation of color-location binding in infants' visual short-term memory.

Two experiments examined 8- and 10-month-old infants' ( = 71) binding of object identity (color) and location information in visual short-term memory (VSTM) using a . Building on previous work using the task, we confirmed that 8- and 10-month-old infants are sensitive to changes in binding between identity and location in VSTM. Further, we demonstrated that infants recognize specifically changed in these events.

Developmental Expression of Claudins in the Mammary Gland.

Claudins are a large family of membrane proteins whose classic function is to regulate the permeability of tight junctions in epithelia. They are tetraspanins, with four alpha-helices crossing the membrane, two extracellular loops, a short cytoplasmic N-terminus and a longer and more variable C-terminus. The extracellular ends of the helices are known to undergo side-to-side (cis) interactions that allow the formation of claudin polymers in the plane of the membrane.

Claudin-4 activity in ovarian tumor cell apoptosis resistance and migration.

Background: Claudin-4 is a transmembrane protein expressed at high levels in the majority of epithelial ovarian tumors, irrespective of subtype, and has been associated with tumor cells that are both chemoresistant and highly mobile. The objective of this study was to determine the functional role that claudin-4 plays in apoptosis resistance and migration as well as the therapeutic utility of targeting claudin-4 activity with a small mimic peptide.

Methods: We examined claudin-4 activity in human ovarian tumor cell lines (SKOV3, OVCAR3, PEO4) using in vitro caspase and scratch assays as well as an in vivo mouse model of ovarian cancer.

Characterization of choline transporters in the human placenta over gestation.

Introduction: The developing fetus relies on the maternal blood supply to provide the choline it requires for making membrane lipids, synthesizing acetylcholine, and performing important methylation reactions. It is vital, therefore, that the placenta is efficient at transporting choline from the maternal to the fetal circulation. Although choline transporters have been found in term placenta samples, little is known about what cell types express specific choline transporters and how expression of the transporters may change over gestation.

Developmental changes in visual short-term memory in infancy: evidence from eye-tracking.

We assessed visual short-term memory (VSTM) for color in 6- and 8-month-old infants (n = 76) using a one-shot change detection task. In this task, a sample array of two colored squares was visible for 517 ms, followed by a 317-ms retention period and then a 3000-ms test array consisting of one unchanged item and one item in a new color. We tracked gaze at 60 Hz while infants looked at the changed and unchanged items during test.

Claudins play a role in normal and tumor cell motility.

Background: Claudins are key integral proteins of the tight junction. Although they play an essential role in controlling paracellular diffusion in epithelia, increasing evidence supports a role for these proteins in non-barrier forming activities. To elucidate a potential function for claudins outside of their traditional role in tight junctions, subcellular localization of claudin-4 was determined in normal mammary epithelial cells as well as breast and ovarian cancer cell lines and the effects of a claudin mimic peptide on cell motility were determined.

Using infrared eye-tracking to explore ordinal numerical processing in toddlers with Fragile X Syndrome.

Background: Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and non-idiopathic autism. Individuals with FXS present with a behavioral phenotype of specific and selective deficits in an array of cognitive skills. Disruption of number processing and arithmetic abilities in higher-functioning adults and female adolescents with FXS has been well established.

Rapid and highly specific screening for NPM1 mutations in acute myeloid leukemia.

NPM1 mutations, the most frequent molecular alterations in acute myeloid leukemia (AML), have become important for risk stratification and treatment decisions for patients with normal karyotype AML. Rapid screening for NPM1 mutations should be available shortly after diagnosis. Several methods for detecting NPM1 mutations have been described, most of which are technically challenging and require additional laboratory equipment.

The feasibility of detecting neuropsychologic and neuroanatomic effects of type 1 diabetes in young children.

Objective: To determine if frequent exposures to hypoglycemia and hyperglycemia during early childhood lead to neurocognitive deficits and changes in brain anatomy.

Research Design And Methods: In this feasibility, cross-sectional study, young children, aged 3 to 10 years, with type 1 diabetes and age- and sex-matched healthy control (HC) subjects completed neuropsychologic (NP) testing and magnetic resonance imaging (MRI) scans of the brain.

Results: NP testing and MRI scanning was successfully completed in 98% of the type 1 diabetic and 93% of the HC children.

A D-peptide analog of the second extracellular loop of claudin-3 and -4 leads to mislocalized claudin and cellular apoptosis in mammary epithelial cells.

Claudins are cell adhesion proteins thought to mediate cell-cell contacts at the tight junction. Although a major role of claudins is to control paracellular diffusion, increasing evidence suggests that they may also function in tumor progression. To examine the role of the second extracellular loop in cell adhesion, a small peptide was designed, which mimics a conserved sequence, DFYNP, within specific 'classic' claudin subtypes.

Disruption of occludin function in polarized epithelial cells activates the extrinsic pathway of apoptosis leading to cell extrusion without loss of transepithelial resistance.

Background: Occludin is a tetraspanin protein normally localized to tight junctions. The protein interacts with a variety of pathogens including viruses and bacteria, an interaction that sometimes leads to its extrajunctional localization.

Results: Here we report that treatment of mammary epithelial monolayers with a circularized peptide containing a four amino acid sequence found in the second extracellular loop of occludin, LHYH, leads to the appearance of extrajunctional occludin and activation of the extrinsic apoptotic pathway.

Calcium elevation in mitochondria is the main Ca2+ requirement for mitochondrial permeability transition pore (mPTP) opening.

We have investigated in detail the role of intra-organelle Ca2+ content during induction of apoptosis by the oxidant menadione while changing and monitoring the Ca2+ load of endoplasmic reticulum (ER), mitochondria, and acidic organelles. Menadione causes production of reactive oxygen species, induction of oxidative stress, and subsequently apoptosis. In both pancreatic acinar and pancreatic tumor AR42J cells, menadione was found to induce repetitive cytosolic Ca2+ responses because of the release of Ca2+ from both ER and acidic stores.

Longitudinal brain volume changes in preterm and term control subjects during late childhood and adolescence.

Objective: Although preterm very low birth weight infants have a high prevalence of neuroanatomical abnormalities when evaluated at term-equivalent age, patterns of brain growth in prematurely born infants during school age and adolescence remain largely unknown. Our goal was to test the hypothesis that preterm birth results in long-term dynamic changes in the developing brain.

Methods: We performed serial volumetric MRI studies at ages 8 and 12 years in 55 preterm infants born weighing 600 to 1250 g and 20 term control children who participated in the follow-up component of a prospective, randomized, placebo-controlled intraventricular hemorrhage prevention study.

Disruption of the Cox-1 gene slows repair of microscopic lesions in the mouse gastric epithelium.

Cyclooxygenase-1 (Cox-1) contributes to gastric defense of healthy tissue, but the role in the protection of the gastric epithelium after minor, acute damage has been difficult to study in vivo. Using 710-nm two-photon light absorption to create microscopic gastric damage in anesthetized mice with the gastric mucosal surface surgically exposed and perfused on the microscope stage, the acute response of surface cells to injury could be monitored using in vivo microscopy within seconds after injury. Using exogenous (Cl-NERF) and endogenous fluorophores, extracellular pH and cell death were monitored in real time during the entire damage and repair cycle.

Caspase-8-mediated apoptosis induced by oxidative stress is independent of the intrinsic pathway and dependent on cathepsins.

Cell-death programs executed in the pancreas under pathological conditions remain largely undetermined, although the severity of experimental pancreatitis has been found to depend on the ratio of apoptosis to necrosis. We have defined mechanisms by which apoptosis is induced in pancreatic acinar cells by the oxidant stressor menadione. Real-time monitoring of initiator caspase activity showed that caspase-9 (66% of cells) and caspase-8 (15% of cells) were activated within 30 min of menadione administration, but no activation of caspase-2, -10, or -12 was detected.