Experiences and concerns of parents of children with a 16p11.2 deletion or duplication diagnosis: a reflexive thematic analysis.

Background: 16p11.2 proximal deletion and duplication syndromes (Break points 4-5) (593KB, Chr16; 29.6-30.

Implementation of single IRB review for multisite human subjects research: Persistent challenges and possible solutions.

Revisions to the Common Rule and NIH policy require the use of a single Institutional Review Board (sIRB) for the review of most federally funded, multisite research, with the intent of streamlining the review process. However, since initial implementation in 2018, many IRBs and institutions continue to struggle with the logistics of implementing this requirement. In this paper, we report the findings of a workshop held in 2022 to examine why sIRB review remains problematic and propose possible solutions.

Impaired tumor necrosis factor-α secretion by CD4 T cells during respiratory syncytial virus bronchiolitis associated with recurrent wheeze.

Background: Infants with severe respiratory syncytial virus (RSV) bronchiolitis have an increased risk of recurrent wheezing and asthma. We aimed to evaluate the relationships between regulatory T cell (Treg) percentage and cytokine production of in vitro-stimulated CD4+ T cells during acute bronchiolitis and the development of recurrent wheezing in the first 3 years of life.

Methods: We obtained peripheral blood from 166 infants hospitalized with their first episode of RSV-confirmed bronchiolitis.

An obligatory role for club cells in preventing obliterative bronchiolitis in lung transplants.

Obliterative bronchiolitis (OB) is a poorly understood airway disease characterized by the generation of fibrotic bronchiolar occlusions. In the lung transplant setting, OB is a pathological manifestation of bronchiolitis obliterans syndrome (BOS), which is a major impediment to long-term recipient survival. Club cells play a key role in bronchiolar epithelial repair, but whether they promote lung transplant tolerance through preventing OB remains unclear.

Regulatory T cell subsets are differentially dependent on CD28 for their proliferation.

It is thought that CD28 plays a crucial role in the maintenance of regulatory T cell (Treg) pool size through promoting the development and proliferation of these cells. However, recently we found that the dependency on CD28 co-stimulation for their development is different between Treg subsets, thymus-derived Tregs (tTregs, CD28-dependent) and peripherally-derived Tregs (pTregs, CD28-independent), suggesting that CD28 may also have differential influences on the homeostasis of each Treg subset. Here, we demonstrated that both Treg subsets were reduced in secondary lymphoid organs of CD28 deficient mice, and that this reduction was due to impaired proliferation in both Treg subsets by the intrinsic CD28 defect.

Functional analysis of acquired CD28 mutations identified in cutaneous T cell lymphoma.

CD28 is the major costimulatory receptor on T cells regulating proliferation, survival and effector function. Acquired mutations in the extracellular domain of CD28 have been identified in patients with cutaneous T cell lymphoma, angioimmunoblastic T cell lymphoma and other T cell neoplasms, suggesting it may contribute to disease pathogenesis. We used a heterologous system in which mutant human CD28 was expressed on primary murine T cells deficient in CD28 to ascertain how specific mutations identified in a genetic screen of patients with cutaneous T cell lymphoma affected normal T cell function.

Food and microbiota in the FDA regulatory framework.

Ongoing efforts to develop microbiota-directed foods (MDF) provide potentially new ways for improving health status. A MDF could alter the structural and functional configuration of a consumer’s gut microbial community, provide substrates for microbial transformation to biomolecules necessary for a healthy state, or act through a combination of these mechanisms. The development of MDFs promises to expand our view of ‘essential nutrients’ and prompt questions about how they should be classified and regulated.

Interleukin 7 immunotherapy improves host immunity and survival in a two-hit model of Pseudomonas aeruginosa pneumonia.

Patients with protracted sepsis develop impaired immunity, which predisposes them to acquiring secondary infections. One of the most common and lethal secondary infections is Pseudomonas aeruginosa pneumonia. Immunoadjuvant therapy is a promising approach to reverse sepsis-induced immunosuppression and improve morbidity and mortality from secondary infections.

Land cover change and carbon emissions over 100 years in an African biodiversity hotspot.

Agricultural expansion has resulted in both land use and land cover change (LULCC) across the tropics. However, the spatial and temporal patterns of such change and their resulting impacts are poorly understood, particularly for the presatellite era. Here, we quantify the LULCC history across the 33.

Social cognitive deficits and biases in maltreated adolescents in U.K. out-of-home care: Relation to disinhibited attachment disorder and psychopathology.

Children entering out-of-home (OoH) care have often experienced multiple forms of maltreatment and are at risk of psychiatric disorder and poor long-term outcome. Recent evidence shows high rates of disinhibited attachment disorder (DAD) among maltreated adolescents in U.K.

CD28 Promotes Plasma Cell Survival, Sustained Antibody Responses, and BLIMP-1 Upregulation through Its Distal PYAP Proline Motif.

In health, long-lived plasma cells (LLPC) are essential for durable protective humoral immunity, and, conversely, in disease are a major source of pathogenic Abs in autoimmunity, graft rejection, and allergy. However, the molecular basis for their longevity is largely unknown. We have recently found that CD28 signaling in plasma cells (PC) is essential for sustaining Ab titers, by supporting the survival of LLPC, but not short-lived PC (SLPC).

Walk on the wild side: estimating the global magnitude of visits to protected areas.

How often do people visit the world's protected areas (PAs)? Despite PAs covering one-eighth of the land and being a major focus of nature-based recreation and tourism, we don't know. To address this, we compiled a globally-representative database of visits to PAs and built region-specific models predicting visit rates from PA size, local population size, remoteness, natural attractiveness, and national income. Applying these models to all but the very smallest of the world's terrestrial PAs suggests that together they receive roughly 8 billion (8 x 109) visits/y-of which more than 80% are in Europe and North America.

Interleukin-7 and anti-programmed cell death 1 antibody have differing effects to reverse sepsis-induced immunosuppression.

Sepsis remains a major cause of morbidity and mortality in most intensive care units. Protracted sepsis can evolve into a state of profound immunosuppression characterized by secondary infections, frequently with opportunistic-type pathogens. Immunoadjuvant therapy is currently being evaluated as a novel treatment for patients with sepsis.

Reactivation of multiple viruses in patients with sepsis.

A current controversy is whether patients with sepsis progress to an immunosuppressed state. We hypothesized that reactivation of latent viruses occurred with prolonged sepsis thereby providing evidence of clinically-relevant immunosuppression and potentially providing a means to serially-monitor patients' immune status. Secondly, if viral loads are markedly elevated, they may contribute to morbidity and mortality.

Quantifying and understanding carbon storage and sequestration within the Eastern Arc Mountains of Tanzania, a tropical biodiversity hotspot.

Background: The carbon stored in vegetation varies across tropical landscapes due to a complex mix of climatic and edaphic variables, as well as direct human interventions such as deforestation and forest degradation. Mapping and monitoring this variation is essential if policy developments such as REDD+ (Reducing Emissions from Deforestation and Forest Degradation) are to be known to have succeeded or failed.

Results: We produce a map of carbon storage across the watershed of the Tanzanian Eastern Arc Mountains (33.

Cutting edge: A double-mutant knockin of the CD28 YMNM and PYAP motifs reveals a critical role for the YMNM motif in regulation of T cell proliferation and Bcl-xL expression.

CD28 is a critical regulator of T cell function, augmenting proliferation, cytokine secretion, and cell survival. Our previous work using knockin mice expressing point mutations in CD28 demonstrated that the distal proline motif was primarily responsible for much of CD28 function, whereas in marked contrast to prior studies, mutation of the PI3K-binding motif had little discernible effect. In this study, we examined the phenotype of mice in which both motifs are simultaneously mutated.

Costimulation via the tumor-necrosis factor receptor superfamily couples TCR signal strength to the thymic differentiation of regulatory T cells.

Regulatory T cells (Treg cells) express members of the tumor-necrosis factor (TNF) receptor superfamily (TNFRSF), but the role of those receptors in the thymic development of Treg cells is undefined. We found here that Treg cell progenitors had high expression of the TNFRSF members GITR, OX40 and TNFR2. Expression of those receptors correlated directly with the signal strength of the T cell antigen receptor (TCR) and required the coreceptor CD28 and the kinase TAK1.

Using changes in agricultural utility to quantify future climate-induced risk to conservation.

Much of the biodiversity-related climate change impacts research has focused on the direct effects to species and ecosystems. Far less attention has been paid to the potential ecological consequences of human efforts to address the effects of climate change, which may equal or exceed the direct effects of climate change on biodiversity. One of the most significant human responses is likely to be mediated through changes in the agricultural utility of land.

A detailed phenotypic analysis of immune cell populations in the bronchoalveolar lavage fluid of atopic asthmatics after segmental allergen challenge.

Background: Atopic asthma is characterized by intermittent exacerbations triggered by exposure to allergen. Exacerbations are characterized by an acute inflammatory reaction in the airways, with recruitment of both innate and adaptive immune cells. These cell populations as well as soluble factors are critical for initiating and controlling the inflammatory processes in allergic asthma.

The changing immune system in sepsis: is individualized immuno-modulatory therapy the answer?

Sepsis remains the leading cause of death in most intensive care units. Advances in understanding the immune response to sepsis provide the opportunity to develop more effective therapies. The immune response in sepsis can be characterized by a cytokine-mediated hyper-inflammatory phase, which most patients survive, and a subsequent immune-suppressive phase.

CTLA4Ig inhibits effector T cells through regulatory T cells and TGF-β.

The CD28 costimulatory receptor is a critical regulator of T cell function, making it an attractive therapeutic target for the treatment of immune-mediated diseases. CTLA4Ig, now approved for use in humans, prevents naive T cell activation by binding to B7 proteins and blocking engagement of CD28. However, CTLA4Ig suppresses inflammation even if administered when disease is established, suggesting alternative mechanisms.