Andreas D Schenk

Plain English
Using a national registry of 88,603 liver transplant recipients, researchers compared post-transplant outcomes between undocumented immigrants and US citizens. After statistical adjustment for differences in patient characteristics, survival outcomes were equivalent between groups despite initial apparent differences. The findings support equitable access to liver transplantation for undocumented immigrants.

Plain English
Researchers tested whether giving IL-2 complexes that preferentially expand regulatory T cells could prolong heart transplant survival in mice. IL-2 complex treatment extended allograft survival, reduced donor-specific antibody production, and increased regulatory T cell populations at key immune sites. When combined with short-term tacrolimus, some recipients achieved indefinite graft survival without ongoing immunosuppression.

Plain English
This study examined whether normothermic machine perfusion (NMP) for donation after circulatory death liver transplants reduces postoperative costs at a single center. NMP reduced early allograft dysfunction and postreperfusion syndrome compared to cold storage, but did not decrease total postoperative direct costs. The benefit of NMP lies in expanding the usable donor pool, reducing wait times, and improving clinical outcomes rather than cutting hospital costs.

Plain English
Researchers tested whether kidney transplant patients who needed the blood pressure drug midodrine before transplant had worse outcomes. Patients on midodrine before transplant had dramatically lower 1-year graft survival (79% vs 96%) and patient survival (86% vs 97%) compared to those who did not need it. Pretransplant midodrine use is a potential marker of underlying cardiovascular fragility that predicts inferior transplant outcomes.

Plain English
Using a mouse model of hemophagocytic lymphohistiocytosis (HLH), an aggressive inflammatory syndrome, researchers tested whether inhibiting PRMT5, a protein that drives T-cell inflammation, could control the disease. PRMT5 inhibition with the drug PRT382 reduced spleen and liver enlargement, normalized inflammatory cytokines including interferon-gamma and IL-6, restored T and NK cell counts, and reduced myeloid cell expansion. PRMT5 is a promising target for treating HLH and potentially other hyperinflammatory conditions.

Plain English
This study asked whether liver grafts from donors with hepatitis C who died after cardiac arrest (HCV+DCD) have acceptable outcomes. HCV-positive DCD grafts had 1-year graft survival comparable to standard donation-after-brain-death grafts with or without HCV. Centers should expand acceptance of HCV+DCD livers to grow the donor pool without sacrificing early outcomes.

Plain English
Researchers analyzed national kidney transplant data to identify what drives long waiting times and whether the 2021 kidney allocation policy change (KAS250) helped. Waiting time was most prolonged in patients who only accepted HCV-negative kidneys or low-risk (KDPI <85%) organs, adding over 20 and 10 months respectively. KAS250 reduced wait time disparities but at the cost of longer cold ischemia times and higher delayed graft function rates.

Plain English
A national survey of US liver transplant centers found wide variation in how centers define and manage donation after circulatory death (DCD) liver transplants. Critical parameters like donor warm ischemia time definition, acceptable donor age, and cold ischemia cutoffs varied substantially across the 42 centers surveyed. Standardizing DCD practices based on national outcome data would improve graft utilization and consistency.

Plain English
This review examined liver transplantation as a treatment for both primary liver cancers (hepatocellular carcinoma, cholangiocarcinoma) and metastatic tumors (colorectal liver metastases, neuroendocrine tumors). Transplantation is well-established for hepatocellular carcinoma and selected patients with bile duct cancer, and is increasingly being used for metastatic disease from colorectal and neuroendocrine primaries. Optimal patient selection criteria and ethical organ allocation questions remain active areas of debate.

Plain English
Researchers developed and validated a composite "textbook outcome" metric for heart transplantation that captures multiple dimensions of a good recovery. Patients who achieved textbook outcome had significantly better long-term survival than those who did not, and the metric revealed that 45% of heart transplant recipients achieved it. Textbook outcome offers a richer measure of program quality than 1-year survival alone.

Plain English
Researchers interviewed 38 kidney transplant recipients about their experiences during the COVID-19 pandemic and their views on vaccination. Most patients, vaccinated or not, used masks and avoided crowds to protect themselves, while most vaccinated recipients cited their immunocompromised state as their main reason for vaccination. Even among vaccinated recipients, concerns persisted about inadequate testing of COVID vaccines specifically in transplant patients.

Plain English
This review updated the evidence for liver transplantation as treatment for hepatocellular carcinoma, metastatic colorectal cancer, cholangiocarcinoma, and neuroendocrine tumors. Transplant oncology is evolving rapidly as better understanding of tumor and transplant immunology has expanded eligibility criteria beyond traditional indications. The field continues to debate patient selection, organ allocation ethics, and the role of living donors in these complex cases.

Plain English
Researchers identified a class of compounds called cyanotriazoles that kill trypanosomes—the parasites causing Chagas disease and sleeping sickness—by locking their topoisomerase II enzyme onto broken DNA strands. The compounds worked in mouse models of both diseases and completely cured infections. Selective inhibition of the trypanosomal form of this enzyme, which differs structurally from the human version, is the basis for their selective toxicity.

Plain English
This systematic review and meta-analysis of 59 publications found that clots forming in the heart or lungs during liver transplantation occur in about 1.4% of cases and carry a 40% in-hospital mortality. Clots most often appeared at graft reperfusion, and while heparin was effective in early-stage cases, adding tissue plasminogen activator offered diminishing returns. Better risk identification and management protocols are needed for this devastating intraoperative complication.

Plain English
Researchers applied a composite "textbook outcome" metric to 69,165 kidney transplant recipients and found that achieving textbook outcome was associated with nearly 2-fold lower risk of death at 5 years. Living donor recipients achieved textbook outcome 54% of the time versus 32% for deceased donor recipients. The metric identifies 18-24% of centers as underperforming in ways that 1-year survival statistics miss.

Plain English
This 17-center international benchmark study defined outcomes for liver transplantation in patients with early-stage bile duct cancer treated with neoadjuvant chemoradiation. Five-year disease-free survival was 62% after transplant versus 32% after liver resection in matched patients. Transplantation for this indication should be considered a standard option and may actually be superior to surgery in early-stage disease.

Plain English
This case report describes a patient who developed a spinal cord infarction after kidney transplantation, an extremely rare complication with no identifiable cause found on investigation. A thorough literature review found no similar previously reported case. The report highlights that kidney transplant recipients with multiple comorbidities are at risk for unusual perioperative complications.

Plain English
Researchers applied a "textbook outcome" quality metric to 25,887 adult liver transplant recipients and found that only 37.4% achieved it nationally. Patients who did not achieve textbook outcome had 22% higher 5-year mortality, and the composite metric identified 31% of centers as high performing and 21% as below average. Textbook outcome adds meaningful depth to quality assessment beyond 1-year survival.

Plain English
This study examined how the 2020 liver allocation policy change (acuity circles) affected which donors were used at transplant centers with previously high versus low MELD scores. After the policy change, low-MELD centers significantly increased use of less-than-ideal donors, while high-MELD centers shifted toward higher-quality donors. A subset of high-performing centers expanded their transplant volume by broadly increasing acceptance of all donor types including DCD donors.

Plain English
A meta-analysis of 8 studies covering 1,434 pancreas transplant recipients found that patients who developed new donor-specific antibodies after transplant had 4.4 times higher odds of graft failure and 3.4 times higher odds of rejection. The analysis provides clear evidence that post-transplant monitoring for new anti-HLA antibodies is an important component of pancreas transplant care.

Plain English
Structural and biochemical studies revealed that the CRL4 family of ubiquitin ligases is maintained in an inactive state through a tetramerization mechanism in which neighboring subunits block each other's active site. Activation by neddylation disrupts this interaction, releasing the complex into an active dimeric form. This identifies a novel self-inhibitory mechanism for keeping ubiquitin ligases inactive when not needed.

Plain English
Using cryo-electron microscopy at 3.8 Angstrom resolution, researchers determined the structure of the C9orf72-SMCR8 complex, mutations in which cause ALS and frontotemporal dementia. The structure revealed two distinct interfaces between C9orf72 and SMCR8 and showed structural similarities to a known GTPase activating protein complex that helped identify the active site. A coiled-coil region of SMCR8 appears to serve as a scaffold for recruiting other proteins during cell starvation responses.

Plain English
Cryo-EM was used to determine the structure of human Ebp1 bound to the 80S ribosome at 3.3 Angstrom resolution, showing it binds near the peptide exit tunnel. Ebp1 binding to the ribosome was enhanced by the translation inhibitor puromycin, and the protein can rotate around an insert domain to adopt different conformations while remaining attached. This dynamic association suggests Ebp1 can regulate protein synthesis in response to cellular conditions.

Plain English
Cryo-EM structures were determined for the stem cell reprogramming factors OCT4 and SOX2 bound to nucleosomes at two different positions. Depending on where on the nucleosome their binding motif was located, the two transcription factors distorted nucleosomal DNA in different ways to access their sites. OCT4 uses only one of its two DNA-binding domains when engaging DNA in the context of a nucleosome, explaining how these factors access chromatinized genes.

Plain English
Cryo-EM structures of the human 80S ribosome captured at three stages of the elongation cycle revealed that the C-terminal tail of ribosomal protein uS19 contacts transfer RNAs and messenger RNA in the decoding site during translation. This tail changes conformation as the ribosome moves through elongation states, and disease-associated mutations in uS19 increase errors in reading the genetic code. The work identifies a previously unrecognized role for uS19 in ensuring accurate and efficient protein synthesis.

Plain English
CryoFLARE is described as an open-source software platform that performs real-time image processing during cryo-EM data collection, enabling immediate quality feedback so problems can be corrected before extensive data is collected. The system integrates multiple processing algorithms, automatically generates processing reports, and exports data in formats compatible with standard refinement software. It addresses a key bottleneck in cryo-EM workflows that historically required waiting until data collection was complete before assessing quality.

Plain English
This case report describes long-term successful use of belatacept immunosuppression in a patient who received a kidney transplant after a previous heart transplant. Belatacept avoids the kidney toxicity of calcineurin inhibitors, making it particularly useful when preserving kidney function is critical. The report reviews the emerging evidence for belatacept use outside of primary kidney transplantation.

Plain English
A survey of transplant surgeons revisited the safety of travel to retrieve organs from deceased donors and found that 23% of respondents had experienced a travel accident with bodily injury. Despite this, only 7% felt unsafe during procurement travel. As organ allocation policies expand geographic distribution and require longer-distance travel, the transplant field must take procurement safety more seriously.

Plain English
Cryo-EM structures of two related protein complexes—BRCA1-A and BRISC—revealed the molecular basis for how the deubiquitinase BRCC36 is targeted to specific cellular functions. In BRCA1-A, the scaffold protein ABRAXAS sequesters tumor suppressor BRCA1 away from DNA break sites, while in BRISC, the metabolic enzyme SHMT2 blocks BRCC36 activity by preventing access to ubiquitin chains. These findings explain how the same catalytic subunit performs completely different jobs in two distinct complexes.

Plain English
This is a publisher correction to a previously published article fixing reversed 5'/3' labels in a DNA sequence figure and adding missing panel labels. No new scientific findings are presented.

Plain English
Cryo-EM revealed how the UV-DDB protein complex detects DNA damage hidden within nucleosomes, where the histone octamer would normally block access. For lesions buried against the histone core, UV-DDB physically shifts the DNA register of the nucleosome, effectively moving the damage from an inaccessible position to an exposed one before binding. This slide-assisted site exposure mechanism explains how the genome surveillance machinery finds damage that is buried deep within chromatin.

Plain English
Mice lacking both the VISTA and PD-1 immune checkpoint proteins showed greater spontaneous T-cell activation and more severe autoimmune disease than mice missing either checkpoint alone. Combined blockade of VISTA and PD-L1 with antibodies was more effective at clearing tumors than blocking either pathway alone. VISTA and PD-1 operate through distinct, non-redundant mechanisms, providing a rationale for combining therapies targeting both pathways.

Plain English
Comprehensive characterization of mice with the VISTA gene deleted showed that loss of VISTA leads to gradual accumulation of activated T cells and heightened inflammatory responses with age. While VISTA-deficient mice did not develop spontaneous autoimmune disease, crossing them with mice predisposed to autoimmunity dramatically accelerated disease onset and severity. VISTA suppresses T-cell activation through a distinct mechanism from PD-1, and its loss specifically lowers the threshold at which autoimmunity is triggered.

Plain English
In mice lacking CCR5, which impairs regulatory T cell function, kidney grafts with a single MHC class II mismatch that would be spontaneously accepted in normal mice were rejected by CD8 T cells. The CD8 T cells recognized peptides derived from the mismatched MHC class II molecule when presented on class I molecules, a specificity not seen in normal mice. This reveals a novel class of alloreactive T cells that emerge specifically when regulatory T cell suppression is impaired.

Plain English
The OpenStructure software framework is described as an updated, flexible platform for computational structural biology that integrates molecular structures, sequence data, and density maps in a unified environment with 3D visualization. The framework is written in C++ with Python access, licensed under LGPL, and runs on multiple operating systems. It has been used as the foundation for developing other structural biology software tools including IPLT and QMean.

Plain English
A Python-based pipeline was developed to automate the processing of electron diffraction data from 2D protein crystals using the IPLT framework. The pipeline handles merging, scaling, and correction of diffraction patterns through a modular, command-line or GUI interface, with C++ processing code for speed. Validation using aquaporin-0 diffraction data confirmed the pipeline produces results equivalent to classical processing methods.

Plain English
Researchers dissected the functional requirements within the phosphoprotein (P) cofactor of vesicular stomatitis virus RNA polymerase, identifying three distinct elements in its N-terminal domain that each serve a specific role. One element induces a structural change in the large polymerase protein L, a second stimulates processivity (the ability to complete long RNA copies), and a third enables transcription of encapsidated RNA. P is not merely a physical bridge but an active driver of polymerase conformation and function.

Plain English
Molecular dynamics simulations were used to examine how lipids position themselves around the water channel protein aquaporin-0 in a membrane. The acyl chain portions of the lipids were tightly localized around the protein while the head groups were mobile, and protein surface mobility rather than charge was the main determinant of lipid positioning. The simulations validated the crystallographic lipid positions as physiologically relevant and revealed a general mechanism for how membrane proteins organize their surrounding lipid shell.

Plain English
The thermodynamics of zinc binding were measured for three transcription factor peptides with different zinc coordination types using isothermal titration calorimetry. All three bound zinc with similar overall affinity, but peptides with more cysteine ligands had more favorable binding entropy offset by less favorable enthalpy. The results show that cysteine coordination drives the entropy-enthalpy compensation that allows different zinc finger motifs to achieve similar binding affinities through different physical mechanisms.

Plain English
In mouse cardiac transplants, giving anti-LFA-1 antibody on days before and at transplant completely prevented early memory CD8 T cell infiltration into the graft and neutrophil accumulation, extending survival from 8 to 27 days. Delaying treatment to days 3-4 post-transplant failed to block early infiltration. Peritransplant LFA-1 blockade effectively prevents the early memory T cell attack on allografts driven by prior immune sensitization.

Plain English
The Tilted Contrast Imaging Function (TCIF) model is presented for mathematically describing how electron microscopes image tilted samples, where focus varies continuously across the field of view. The paper extends the TCIF to account for astigmatism and provides methods for generating corrected simulated images. Analysis shows that the classical Contrast Transfer Function, which assumes uniform focus, introduces significant artifacts in tilted-sample imaging that TCIF can correct.

Plain English
Electron microscopy was used to obtain the first molecular view of the VSV RNA polymerase large protein L, alone and bound to its phosphoprotein cofactor. L is organized into a ring domain containing the polymerase core, with three globular appendages containing the cap-forming machinery. Binding of the phosphoprotein causes a large conformational rearrangement of L that likely positions the functional domains optimally for transcription.

Plain English
Researchers purified the Machupo arenavirus RNA polymerase (L protein) and used electron microscopy to visualize its architecture and RNA-binding behavior. The L protein has a central ring domain similar to polymerases of double-stranded RNA viruses, and RNA recognition requires both single-stranded RNA and a specific sequence at the genome 3' end. These structural features provide a model for how arenavirus polymerases recognize and replicate their segmented genomes.

Plain English
This methods chapter describes the computational pipeline for processing image and electron diffraction data from 2D protein crystals using Medical Research Council programs, supplemented by 2dx, XDP, and IPLT software. The chapter provides a practical guide to the Fourier space-based crystallographic approaches used in 2D electron crystallography. The workflow produces 3D structural data by combining many electron microscopy images and diffraction patterns.

Plain English
This review summarized the contribution of electron crystallography to understanding aquaporin water channel structure and function, and how aquaporin research in turn drove technical advances in the field. Electron crystallography determined near-atomic resolution structures of multiple aquaporin family members, revealing the mechanisms of water selectivity and solute exclusion. Technical advances in 2D crystal preparation, data collection, and image processing developed for aquaporin work have benefited the entire electron crystallography field.

Plain English
This methods chapter covers the practical steps for collecting high-resolution electron microscopy data from 2D protein crystals, including critical preparation steps such as flattening and staining crystals for imaging. Both image and diffraction data collection protocols are described in detail for recording high-resolution information from tilted specimens. Proper specimen preparation is identified as the most important determinant of data quality.

Plain English
OpenStructure is presented as a modular open-source software framework for computational structural biology built on C++ libraries with full Python accessibility. The platform integrates structural data with sequence information and density maps and includes powerful 3D visualization. It has been used as the foundation for multiple downstream structural biology tools and is designed to be extensible as the field develops new methods.