A CAR enhancer increases the activity and persistence of CAR T cells.

Although chimeric antigen receptor (CAR) T cell therapies have demonstrated promising clinical outcomes, durable remissions remain limited. To extend the efficacy of CAR T cells, we develop a CAR enhancer (CAR-E), comprising a CAR T cell antigen fused to an immunomodulatory molecule. Here we demonstrate this strategy using B cell maturation antigen (BCMA) CAR T cells for the treatment of multiple myeloma, with a CAR-E consisting of the BCMA fused to a low-affinity interleukin 2 (IL-2).

Reviewing Challenges of Predicting Protein Melting Temperature Change Upon Mutation Through the Full Analysis of a Highly Detailed Dataset with High-Resolution Structures.

Predicting the effects of mutations on protein stability is a key problem in fundamental and applied biology, still unsolved even for the relatively simple case of small, soluble, globular, monomeric, two-state-folder proteins. Many articles discuss the limitations of prediction methods and of the datasets used to train them, which result in low reliability for actual applications despite globally capturing trends. Here, we review these and other issues by analyzing one of the most detailed, carefully curated datasets of melting temperature change (ΔTm) upon mutation for proteins with high-resolution structures.

Soil C and N models that integrate microbial diversity.

Industrial agriculture is yearly responsible for the loss of 55-100 Pg of historical soil carbon and 9.9 Tg of reactive nitrogen worldwide. Therefore, management practices should be adapted to preserve ecological processes and reduce inputs and environmental impacts.

Microbial Diversity Indexes Can Explain Soil Carbon Dynamics as a Function of Carbon Source.

Mathematical models do not explicitly represent the influence of soil microbial diversity on soil organic carbon (SOC) dynamics despite recent evidence of relationships between them. The objective of the present study was to statistically investigate relationships between bacterial and fungal diversity indexes (richness, evenness, Shannon index, inverse Simpson index) and decomposition of different pools of soil organic carbon by measuring dynamics of CO2 emissions under controlled conditions. To this end, 20 soils from two different land uses (cropland and grassland) were incubated with or without incorporation of 13C-labelled wheat-straw residue.

Volumes of cochlear nucleus regions in rodents.

The cochlear nucleus receives all the coded information about sound from the cochlea and is the source of auditory information for the rest of the central auditory system. As such, it is a critical auditory nucleus. The sizes of the cochlear nucleus as a whole and its three major subdivisions - anteroventral cochlear nucleus (AVCN), posteroventral cochlear nucleus (PVCN), and dorsal cochlear nucleus (DCN) - have been measured in a large number of mammals, but measurements of its subregions at a more detailed level for a variety of species have not previously been made.

A New Dip Coating Method to Obtain Large-Surface Coatings with a Minimum of Solution.

A new, simple bi-phasic dip-coating method is developed. This method is considered as a great improvement of the technique for research, development and production, since expensive, rare, harmful, or time-evolving solutions can now be easily deposited on large surfaces and on a single side from very little amounts of solution.

Engineering functionality gradients by dip coating process in acceleration mode.

In this work, unique functional devices exhibiting controlled gradients of properties are fabricated by dip-coating process in acceleration mode. Through this new approach, thin films with "on-demand" thickness graded profiles at the submillimeter scale are prepared in an easy and versatile way, compatible for large-scale production. The technique is adapted to several relevant materials, including sol-gel dense and mesoporous metal oxides, block copolymers, metal-organic framework colloids, and commercial photoresists.

Conventional open repair of descending thoracic aortic aneurysms.

Conventional open reconstruction of the descending thoracic aorta is a safe and effective therapy for the management of aneurysms and is the standard by which all other therapies should be compared. Advances in surgical techniques, circulation management, neurocerebral protection, anesthesia, and postoperative management have contributed to significant reductions in morbidity and mortality over the past 50 years. More recently, endovascular stent grafting has begun to supplant conventional open repair based on its ease of performance and a perception of reduced morbidity and mortality.

Forceful evacuation of retained pneumoperitoneum mimics an acute recurrent inguinal hernia.

Background: Laparoscopic exploration of the contralateral side during inguinal herniorrhaphy in infants is becoming popular. We present an unusual complication of this technique, namely forceful evacuation of retained pneumoperitoneum mimicking an acute recurrent hernia.

Methods: A 9-month-old female presented for right inguinal herniorrhaphy.

Role of the thymus and kidney graft in the maintenance of tolerance to heart grafts in miniature swine.

Background: The authors have examined the mechanism whereby co-transplantation of a kidney and heart from the same donor induces and maintains tolerance to both organs in miniature swine.

Methods: Transplants were performed across a major histocompatibility complex class I mismatch, and recipients received cyclosporine for 12 days. Group 1 animals received heart transplants alone (n=5), and all other groups received both heart and kidney allografts.

Indirect recognition of MHC class I allopeptides accelerates lung allograft rejection in miniature swine.

The role of indirect allorecognition in graft rejection is examined in two experiments using a swine lung transplantation model. First, two swine received class I mismatched grafts without immunosuppression; another two recipients were treated postoperatively with cyclosporine (CsA). These swine exhibited acute and chronic rejection, respectively.

Nonoperative management of neonatal splenic rupture.

Neonatal injury of the spleen is an uncommon but serious condition. Although the standard management of children with splenic injury is nonoperative, there is scant evidence in the literature to support handling neonates in the same way. We report a case of neonatal splenic rupture that was managed nonoperatively.

Constitutive expression of major histocompatibility complex class II antigens in pulmonary epithelium and endothelium varies among different species.

We have observed high constitutive levels of class II antigen expression on porcine and human coronary endothelium, but not on the endothelium of rats and mice. This study examines whether a similar interspecies difference exists in the expression of class II molecules on pulmonary epithelium and endothelium. Lung tissues from naïve human, porcine, and rodent sources were stained with the monoclonal antibody ISCR3 and examined by light microscopy.

Induction of tolerance to heart transplants by simultaneous cotransplantation of donor kidneys may depend on a radiation-sensitive renal-cell population.

Background: To determine the mechanism by which cotransplantation of a donor kidney and heart allograft induces tolerance to both organs in miniature swine, we examined the renal elements responsible for tolerance induction.

Methods: Recipients received 12 days of cyclosporine, and transplants were performed across a major histocompatibility complex (MHC) class I mismatch. Group 1 animals received heart transplants (n=5); group 2 animals received heart and kidney allografts with no other manipulation (n=4); group 3 animals received heart transplants and donor-specific renal parenchymal cells (n=4); group 4 animals received heart and kidney allografts from lethally irradiated donors (n=7); group 5 animals received irradiated hearts and nonirradiated kidneys (n=2); group 6 animals received nonirradiated hearts and peripheral blood leukocytes from swine MHC matched to recipients and becoming tolerant to donor antigen (n=2); group 7 animals received nonirradiated hearts and donor-specific peripheral blood monocyte cells (PBMC) (n=2).

Cytokines in immunity and allograft rejection.

Cytokines are highly potent regulatory molecules that are secreted by a variety of cells into the local microenvironment. These chemical messengers participate in the activation and regulation of immune function by a variety of mechanisms, including the stimulation and inhibition of cellular proliferation and differentiation. Cytokines also may have chemotactic activity.

Modeling chronic lung allograft rejection in miniature swine.

Background: The success of lung transplantation has been limited by the perplexing problem of chronic rejection. The development of a large-animal model for the systematic study of the mechanisms underlying chronic lung rejection has been problematic. We have developed a new preclinical model of chronic lung rejection using MHC-inbred miniature swine.