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Theses reviewed in this issue include "A Rapid Lipid-Based Approach for Normalization of Quantum Dot-Detected Biomarker Expression on Extracellular Vesicles in Complex Biological Samples," "Cancer Dynamics Under a Chemotherapeutic Stress Gradient Using a Microfluidic In Vitro Tumor Environment," "Cells Exhibiting Strong P16ink4a Promoter Activation In Vivo Display Features of Senescence," "HLA-G Dimer Prolongs Kidney Allograft Survival by Inhibiting CD8 + T Cell Activation and Granzyme B Expression," "Lysophosphatidic Acid Suppression of CD8 T Cell Signaling and Function," and "Targeting Therapeutic T Cells to the Bone Marrow Niche."

Theses reviewed in this issue include "Engineering Protein Disaggregases to Counter Alpha-Synuclein and Amyloid-Beta Neurotoxicity," "Hyperglycaemia Induced Immunomodulation of Macrophages in Diabetic Vascular Disease," "Microvasculature-on-a-Chip Systems for Human Disease Modeling," "Senescence Surveillance: The Interplay Between the Immune System and Senescent Cells," "The HMG Transcription Factor TOX Induces a Transcriptional and Epigenetic Program of CD8 + T Cell Exhaustion in Chronic Infection and Cancer," and "Zero to One-Translational Advancements in the Field of Xenotransplantation."

Theses reviewed in this issue include "An Aging Tug of War: The Accumulation of the Spontaneous L-Isoaspartate Modification in Proteins vs. Canonical and Novel Maintenance Pathways," "Cellular and Molecular Mechanisms Underpinning Microglial Activation During Remyelination," "Early Detection of Cancer Metastasis at a Synthetic Pre-Metastatic Niche Using Inverse Spectroscopic Optical Coherence Tomography," "Magnetic Stem Cell Spheroid Microrobots and Their In Vivo Applications," "Reprogramming Human Endothelium to Hematopoietic Stem Cells with Adaptive Immune Function," and "Scaffold-Free Three-Dimensional Bioprints Repair Small Intestine Injuries and Integrate Into Native Intestine."

Theses reviewed in this issue include "Developing the Next Generation of Universal Immune Receptors," "From Synthesis to Pathology: A Bottom-Up Approach to Studying the Role of Advanced Glycation End-Products in Diabetes and Aging," "Hybrid Bioactive Nanoparticles for Modulation of Tumor Microenvironment and Enhancing Radiation and Chemotherapy Efficacy," "In Situ Bioprinting of Planar Biomaterials and Tissues," "Novel AAV Engineering Technology: Identification of Improved AAV Variants for Gene Addition and Genome Engineering in Primary Human Cells," and "Substrate Reduction Therapy for Krabbe Disease and a New Murine Model for Cell-Autonomous Expression of Lysosomal Hydrolases."

Theses reviewed in this issue include "Engineering Efficient and Safe In Situ Genome Regulation via CRISPR-Cas9 for Enabling Gene Therapies," "Investigating the Mechanism of LINE-1 Retrotransposition in Human Cells," "Machine Learning Approaches for Prediction of Kidney Transplant Survival," "Novel Obesity Suppressor Function of the Retinoblastoma Protein Uncovers Cyclin-Dependent Kinase 4 as a Therapeutic Target for Diet-Induced Obesity," "Regeneration of Retinal Neurons from Müller Glia in Adult Mice," and "Reprogramming T Cells to Interrogate Intracellular Disease Signatures."

Theses reviewed in this issue include "Characterization and Purification of Putative Stem Cells from the Adult Murine Pancreas," "Inhibition of TLR4 Minimizes Islet Damage due to Sterile Inflammation and Improves Islet Transplant Outcomes," "Liquefaction of the Brain Following Stroke Shares Multiple Characteristics with Atherosclerosis and Mediates Secondary Neurodegeneration in an Osteopontin-Dependent Mechanism," "Manipulating the Segregation of Human Mitochondrial DNA," "Role of Mitochondria in Plasma Membrane Repair and Pathogenesis of Muscular Dystrophy," and "The Role of Cytosolic Accumulation of Nuclear DNA in Retinal-Pigment Epithelium Dysfunction and Age-Related Macular Degeneration."

Theses reviewed in this issue include "Clearance of Capillary Occlusions Improves Cortical Blood Flow and Cognitive Function in Alzheimer's Mouse Models," "Dermato-Informatic Approaches to Understanding and Improving Lesional Diagnostic Expertise in Cutaneous Oncology," "Furthering the Scope, Understanding, and Application of Proteolysis Targeting Chimera," "Optimization and Application of Synthetic High-Density Lipoprotein (sHDL) System in Atherosclerosis and Glioma Therapy," "Regulatory T Cell Enriching Microparticles for Promoting Tolerance in Vascularized Composite Allotransplantation," and "Tau Prion Strains Induce Distinct Pathological Phenotypes In Vivo ."

Theses reviewed in this issue include "Advanced Imaging Technologies for Combined Biomedical Ultrasound and Photoacoustic Imaging," "Engineering Bispecific Chimeric Antigen Receptors to Improve the Efficacy of Adoptive T-Cell Therapy," "Il-36 Gamma Promotes Anti-Tumor Immunity Through Therapeutic Induction of Tumor-Associated Tertiary Lymphoid Structures," "Investigating the Role of Matrix Vesicles During Aortic Valve Interstitial Cell Calcification," "Local Delivery of Cyclosporine and Erythropoietin Promotes Functional Recovery in a Rodent Model of Stroke Injury by Endogenous Tissue Repair," and "Targeting Primary Cilia-Mediated Mechanotransduction to Promote Whole Bone Formation."

Theses reviewed in this issue include "Automated Analysis of Quantitative Image Biomarkers from Low-Dose Chest CT Scans," "Design, Synthesis, and Delivery of a Self-Cleaving Replicon System Yielding Biologically Active MicroRNAs In Vivo ," "Mechanisms of Physiological Amyloidogenesis," "Programming and Reprogramming Neural Cell Types Using Synthetic Transcription Factors," "Targeted Drug Delivery via Exploitation of the Tumor Microenvironment," and "Towards Clinically-Relevant Cell-Transplant-Based Therapies for the Treatment of Liver Diseases."

Theses reviewed in this issue include "Atrophied Thymus, a Tumor Reservoir for Harboring Melanoma Cells," "Evolutionary Adaptations in Developmental Signaling Pathways Underlie Regenerative Scar-Free Wound Repair in African Spiny Mouse (Genus Acomys )," "Integrated Immunoassays on Paper/Polymer Hybrid Microfluidic Devices for Low-Cost Detection of Disease Biomarkers," "RNA Regulation in the Nervous System: CircRNA Expression Changes During Aging, and Function of the Calm1 Extended 3' UTR Isoform," "The Role of Amylin in Alzheimer's Disease," and "Therapeutic Monoclonal Antibodies to Detect and Halt ATTR Cardiac Amyloidosis and Neuropathy."

Theses reviewed in this issue include "Cancer and Stem Cell Extravasation through Angiopellosis," "Human Chimeric Antigen Receptor Macrophages for Cancer Immunotherapy," "Insights on Alzheimer's Disease Etiology from Network Approaches in Healthy Aging," "Myelin and Glial Pathology in Aging and Cognitive Decline: Evidence for Faulty Myelin Clearance in the Rhesus Monkey," "Phosphatidylserine-Based Nanoparticles for Tolerance Induction Toward Therapeutic Proteins," and "Role of Endothelial Cell Stiffening in Choroidal Atrophy Associated with Dry Age-Related Macular Degeneration."

Theses reviewed in this issue include "Downregulation of the Apelinergic Axis Accelerates Aging, Whereas Its Systemic Restoration Improves the Mammalian Healthspan," "Intracellular Delivery of Exogenous Molecules Via an Ultrahigh Throughput Mechanoporation Microdevice," "Intrinsic and Extrinsic Drivers of Treg Fragility in the Tumor Microenvironment," "Lipid Nanoparticles Based Nanomedicine and Liquid Biopsy in Lung Cancer Therapy and Diagnosis," "Stimuli-Responsive Biomaterials for Drug Delivery to Improve Cancer Immunotherapy and Chronic Wound Healing," and "Zebrafish Extracellular Matrix as a Therapeutic Agent for Adult Mammalian Central Nervous System Regeneration."

Theses reviewed in this issue include "Age-Associated Lamin-B1 Reduction in the Thymic Epithelial Cells and Its Role in Thymic Involution," "Brainstem Structural Integrity in the Progression of Alzheimer's Disease," "Challenging Current Paradigms: Increasing the Efficacy of Radiation Therapy with Novel Radiation Schemes," "Cross-Talk Between the Skeletal Muscle Stem Cells and Endothelial Cells," "Design and Synthesis of Enzyme-MOF (Metal-Organic Framework) Composites for Long-Persistent Biomedical Applications," and "Megakaryocyte-Membrane Wrapped Nanoparticles for Targeted Delivery to Hematopoietic Stem Cells."

Theses reviewed in this issue include "Alpha-Synuclein Oligomers: Cellular Mechanisms and Aspects of Antibody Treatment," "Cx3cr1/cx3cl1 Axis Drives the Migration and Maturation of Oligodendroglia in the Central Nervous System," "Genome-Wide Expression Profiling of Human Circulating Monocytes and Macrophages Identifies Diagnostic and Prognostic Signatures for Cancer Outcomes," "Lysosomal Oxidation of Low Density Lipoproteins," and "The Senescence-Associated Secretory Phenotype Induced by ID1-p16 Axis Contributes to Sorafenib Resistance in Hepatocellular Carcinoma."

Theses reviewed in this issue include Characterization and Modeling of Metabolic Stress Responses in Cellular Aging; Engineering Immunity: Enhancing T Cell Vaccines and Combination Immunotherapies for the Treatment of Cancer; Extracellular Inflammatory Signaling from Dysfunctional Telomeres; High-Throughput Microfluidic Labyrinth for the Label-Free Isolation of circulating tumor cells for Single-Cell Gene Expression Profiling; Oxygen Nanobubbles for Ultrasound-guided Targeting of Cancer Hypoxia; and The Eye as a Window to the Alzheimer's Disease Brain.

Theses reviewed in this issue include "A Thromboresistant Cell-Derived Biomaterial Modification for Vascular Grafts," "Actomyosin Mediated Tension Orchestrates Thermogenic Programs in Adipocytes," "Age-Associated Changes in Intrathymic B Cell Population in Mice," "Endoplasmic Reticulum Stress Is Transmissible Among Cells of the Central Nervous System," "Evaluation of Early Tumor Angiogenesis Using Ultrasound Acoustic Angiography," and "Interactions Between Amyloid-Beta and Microglial Cells."

Theses reviewed in this issue include "Computational Pathology for Quantifying Spatial Heterogeneity in Digital Images of Tissue Sections from Solid Tumors," "Molecular Analysis of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration Brain Tissue Identifies Disease Mechanisms Associated with Repetitive DNA Elements," "Neuroprotective Potential of the N-Terminal Beta Amyloid Peptide Fragment in the Neurodegeneration, Synaptic Dysfunction and Memory Deficits in Models of Alzheimer's Disease," "pH-triggered Self-Assembly of a PEGylated Peptide Amphiphilic Contrast Agent," "Quantitative Approaches for Profiling the T Cell Receptor Repertoire in Human Tissues," and "Regulation and Repair of Neural Stem Cells and the Neurogenic Niche."

Theses reviewed in this issue include "Bowties, Barcodes, and DNA Origami: A Novel Approach for Paired-Chain Immune Receptor Repertoire Analysis," "Development of Canine Chimeric Antigen Receptor T Cell Therapy for Treatment & Translation," "Endocytic Vesicle Rupture in the Pathogenesis and Propagation of Neurodegenerative Proteinopathies," "Exploring Mechanisms of Metastasis Suppression in Metastatic Melanoma," "Polymer and Nucleic Acid Self-Assemblies: Properties and Applications at the Biological Interface," and "Towards a Scalable, Biomimetic, Antibacterial Coating."

Theses reviewed in this issue include "Engineering Cellular Input-Output for the Robust Control of Mammalian Cell-Based Therapies"; "Enzyme-Instructed Self-Assembly (EISA) Selectively Targets Cancer Cells"; "Exploration of helminth-derived immunoregulatory molecules as options for therapeutic intervention in allograft rejection and autoimmune disease"; "Expression of the Medial HOXA genes is indispensible for self-renewal in human hematopoietic stem cells"; "Gamma frequency entrainment attenuates amyloid load and modifies microglia"; and "Heterogeneous Distribution of Microvascular Blood Flow Contributes to Impaired Skeletal Muscle Oxygenation in Diabetes".

During animal cell division, the central spindle, an anti-parallel microtubule bundle structure formed between segregating chromosomes during anaphase, cooperates with astral microtubules to position the cleavage furrow. Because the central spindle is the only structure linking the two halves of the mitotic spindle, it is under mechanical tension from dynein-generated cortical pulling forces, which determine spindle positioning and drive chromosome segregation through spindle elongation. The central spindle should be flexible enough for efficient chromosome segregation while maintaining its structural integrity for reliable cytokinesis. How the cell balances these potentially conflicting requirements is poorly understood. Here, we demonstrate that the central spindle in C. elegans embryos has a resilient mechanism for recovery from perturbations by excess tension derived from cortical pulling forces. This mechanism involves the direct interaction of two different types of conserved microtubule bundlers that are crucial for central spindle formation, PRC1 and centralspindlin.

In this viewpoint, we describe the strategies for engineered negligible senescence (SENS) concept--a simple and appealing model for the design of therapeutic interventions able to meaningfully and persistently reverse the deleterious effects of aging. We go on to outline how current or foreseeable biotechnologies could feasibly be employed to repair every currently identified category of pathogenic damage that accumulates over a human lifespan. Then, briefly, we explain why this goal is not only ethically sound, but can in fact be considered to verge on an ethical obligation. Finally, we review recent progress in some key areas of the SENS platform, including proof-of-concept research sponsored by the SENS Foundation, a charity based in California., (Copyright © 2012 S. Karger AG, Basel.)

A major type of unwanted cells that accumulate in aging are anergic cytotoxic T cells. These cells often have virus-specific T cell receptors, as well as other surface markers that distinguish them from their youthful counterparts, and they are thought to play a major role in the decline of the immune system with age. Here we consider two surface markers thought to define these cells in mice, CD8 and Killer cell lectin-like receptor G1 (KLRG1), and a means we developed to remove these cells from the blood of aged C57BL/6 mice. Using antibodies with magnetic nanoparticles linked to their Fc domains, we first developed a method to use magnets to filter out the unwanted cells from the blood and later constructed a device that does this automatically. We demonstrated that this device could reduce the KLRG1-positive CD8 cell count in aged mouse blood by a factor of 7.3 relative to the total CD8 cell compartment, reaching a level typically seen only in very young animals.