Proteins That Promote Filopodia Stability, but Not Number, Lead to More Axonal-Dendritic Contacts

Dendritic filopodia are dynamic protrusions that are thought to play an active role in synaptogenesis and serve as precursors to spine synapses. However, this hypothesis is largely based on a temporal correlation between filopodia formation and synaptogenesis. We investigated the role of filopodia in synapse formation by contrasting the roles of molecules that affect filopodia elaboration and motility, versus those that impact synapse induction and maturation. We used a filopodia inducing motif that is found in GAP-43, as a molecular tool, and found this palmitoylated motif enhanced filopodia number and motility, but reduced the probability of forming a stable axon-dendrite contact. Conversely, expression of neuroligin-1 (NLG-1), a synapse inducing cell adhesion molecule, resulted in a decrease in filopodia motility, but an increase in the number of stable axonal contacts. Moreover, RNAi knockdown of NLG-1 reduced the number of presynaptic contacts formed. Postsynaptic scaffolding proteins such as Shank1b, a protein that induces the maturation of spine synapses, increased the rate at which filopodia transformed into spines by stabilization of the initial contact with axons. Taken together, these results suggest that increased filopodia stability and not density, may be the rate-limiting step for synapse formation

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Comparative Treatment Outcomes for Patients With Idiopathic Subglottic Stenosis.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadImportance: Surgical treatment comparisons in rare diseases are difficult secondary to the geographic distribution of patients. Fortunately, emerging technologies offer promise to reduce these barriers for research. Objective: To prospectively compare the outcomes of the 3 most common surgical approaches for idiopathic subglottic stenosis (iSGS), a rare airway disease. Design, setting, and participants: In this international, prospective, 3-year multicenter cohort study, 810 patients with untreated, newly diagnosed, or previously treated iSGS were enrolled after undergoing a surgical procedure (endoscopic dilation [ED], endoscopic resection with adjuvant medical therapy [ERMT], or cricotracheal resection [CTR]). Patients were recruited from clinician practices in the North American Airway Collaborative and an online iSGS community on Facebook. Main outcomes and measures: The primary end point was days from initial surgical procedure to recurrent surgical procedure. Secondary end points included quality of life using the Clinical COPD (chronic obstructive pulmonary disease) Questionnaire (CCQ), Voice Handicap Index-10 (VHI-10), Eating Assessment Test-10 (EAT-10), the 12-Item Short-Form Version 2 (SF-12v2), and postoperative complications. Results: Of 810 patients in this cohort, 798 (98.5%) were female and 787 (97.2%) were white, with a median age of 50 years (interquartile range, 43-58 years). Index surgical procedures were ED (n = 603; 74.4%), ERMT (n = 121; 14.9%), and CTR (n = 86; 10.6%). Overall, 185 patients (22.8%) had a recurrent surgical procedure during the 3-year study, but recurrence differed by modality (CTR, 1 patient [1.2%]; ERMT, 15 [12.4%]; and ED, 169 [28.0%]). Weighted, propensity score-matched, Cox proportional hazards regression models showed ED was inferior to ERMT (hazard ratio [HR], 3.16; 95% CI, 1.8-5.5). Among successfully treated patients without recurrence, those treated with CTR had the best CCQ (0.75 points) and SF-12v2 (54 points) scores and worst VHI-10 score (13 points) 360 days after enrollment as well as the greatest perioperative risk. Conclusions and relevance: In this cohort study of 810 patients with iSGS, endoscopic dilation, the most popular surgical approach for iSGS, was associated with a higher recurrence rate compared with other procedures. Cricotracheal resection offered the most durable results but showed the greatest perioperative risk and the worst long-term voice outcomes. Endoscopic resection with medical therapy was associated with better disease control compared with ED and had minimal association with vocal function. These results may be used to inform individual patient treatment decision-making.Patient-Centered Outcomes Research Institute - PCOR

Infant Feeding Decision-Making and the Influences of Social Support Persons Among First-Time African American Mothers

Background While breast milk is considered the gold standard of infant feeding, a majority of African American mothers are not exclusively breastfeeding their newborn infants. Objective The overall goal of this critical ethnographic research study was to describe infant feeding perceptions and experiences of African American mothers and their support persons. Methods Twenty-two participants (14 pregnant women and eight support persons) were recruited from public health programs and community based organizations in northern California. Data were collected through field observations, demographic questionnaires, and multiple in-person interviews. Thematic analysis was used to identify key themes. Results Half of the mothers noted an intention to exclusively breastfeed during the antepartum period. However, few mothers exclusively breastfed during the postpartum period. Many participants expressed guilt and shame for not being able to accomplish their antepartum goals. Life experiences and stressors, lack of breastfeeding role models, limited experiences with breastfeeding and lactation, and changes to the family dynamic played a major role in the infant feeding decision making process and breastfeeding duration. Conclusions for Practice Our observations suggest that while exclusivity goals were not being met, a considerable proportion of African American women were breastfeeding. Future interventions geared towards this population should include social media interventions, messaging around combination feeding, and increased education for identified social support persons. Public health measures aimed at reducing the current infant feeding inequities would benefit by also incorporating more culturally inclusive messaging around breastfeeding and lactation

Marginal Zone B-Cell Depletion Impairs Murine Host Defense against Borrelia burgdorferi Infection▿

Marginal zone B (MZB) cells are a B-cell subset that produces T-cell-independent antibodies to blood-borne antigens. In this study, we examined the effects of MZB cell depletion on the immune response to the Lyme disease spirochete Borrelia burgdorferi, an extracellular pathogen for which T-cell-independent antibody is an important host defense. MZB cell depletion of C3H/HeJ mice using monoclonal antibody to LFA-1 and α4β1 integrins reduced B. burgdorferi-specific immunoglobulin M (IgM) titers, enhanced pathogen burden, and led to more severe arthritis assessed within the first 2 weeks of infection. In addition, MZB cell-depleted mice had reduced levels of B. burgdorferi-specific IgG, which correlated with diminished splenic CD4+ T-cell-activation, proliferation, and cytokine production. Passive transfer of immune mouse serum from infected control mice into infected MZB cell-depleted mice reduced pathogen burden but did not alter the expression of T-cell activation markers on splenic CD4+ T cells. These findings demonstrate that MZB cells not only are a source of pathogen-specific IgM important for limiting spirochete burden and pathology but also play a prominent role in the priming of splenic T-cell responses to a blood-borne pathogen

Breastfeeding and use of social media among first-time African American mothers.

ObjectiveTo describe the use of social media during the antepartum and postpartum periods among first-time African American mothers and their support persons.DesignA qualitative critical ethnographic research design within the contexts of family life course development theory and Black feminist theory.SettingParticipants were recruited from community-based, public health, and home visiting programs.ParticipantsA purposive sample was recruited, consisting of 14 pregnant African American women and eight support persons.MethodsPregnant and postpartum African American women and their support persons were interviewed separately during the antepartum and postpartum periods. Data were analyzed thematically.ResultsParticipants frequently used social media for education and social support and searched the Internet for perinatal and parenting information. Most participants reported using at least one mobile application during their pregnancies and after giving birth. Social media were typically accessed through smartphones and/or computers using different websites and applications. Although participants gleaned considerable information about infant development from these applications, they had difficulty finding and recalling information about infant feeding.ConclusionSocial media are an important vehicle to disseminate infant feeding information; however, they are not currently being used to full potential. Our findings suggest that future interventions geared toward African American mothers and their support persons should include social media approaches. The way individuals gather, receive, and interpret information is dynamic. The increasing popularity and use of social media platforms offers the opportunity to create more innovative, targeted mobile health interventions for infant feeding and breastfeeding promotion

Adolescent ethanol drinking promotes hyperalgesia, neuroinflammation and serotonergic deficits in mice that persist into adulthood

Khan, K. M., Bierlein-De La Rosa, G., Biggerstaff, N., Selvakumar, G. P., Wang, R., Mason, S., Dailey, M. E., & Marcinkiewcz, C. A. (2023). “Adolescent Ethanol Drinking Promotes Hyperalgesia, Neuroinflammation and Serotonergic Deficits in Mice that Persist into Adulthood.” Brain Behavior and Immunity, 107, 419–431. doi.org/10.1016/j.bbi.2022.07.16

The ambivalence of ridesharing

Ridesharing is quite a popular topic of discussion among transport authority personnel. It is perceived to be a viable alternative to classical modes of transportation, and receives a great deal of political support from transport planners. However, not much objective information is available on ridesharing behaviors. We use travel survey data to study the evolution of the ridesharing market in an urban area. Our study is based on data from four large-scale OD surveys conducted in the Greater Montreal Area (1987, 1993, 1998 and 2003). In the latest survey conducted in Montreal, car passengers were asked to identify the driver who gave them the opportunity to travel in this way. Their answers were classified according to the type of driver; for instance, a member of their household, a neighbor or a co-worker. We use this information to calibrate a model matching car passengers and car drivers belonging to the same household. This will be referred to as IHHR (intra-household ridesharing). Preliminary results reveal that approximately 70% of all trips made by car passengers are the result of IHHR. Furthermore, around 15% of those trips are questionable, in that they were exclusively generated for another individual’s purposes, consequently generating an additional trip for the journey back home. Moreover, this percentage increased over time. Objective data regarding ridesharing and its evolution in an urban area will undoubtedly help decision makers gain a clearer profile of this means of travel and help to realign attitudes on the issue. Copyright Springer Science+Business Media, LLC 2007Carsharing, Greater Montreal Area (GMA), Origin–destination surveys, Ridesharing, Sustainable transportation,