Thyroid hormone protects human lung epithelial cells from cold preservation and warm reperfusion-induced injury.

Background: Cellular stress associated with static-cold storage (SCS) and warm reperfusion of donor lungs can contribute to ischemia-reperfusion (IR) injury during transplantation. Adding cytoprotective agents to the preservation solution may be conducive to reducing graft deterioration and improving post-transplant outcomes.

Methods: SCS and warm reperfusion were simulated in human lung epithelial cells (BEAS-2B) by exposing cells to low potassium dextran glucose solution at 4 °C for different periods and then switching back to serum-containing culture medium at 37 °C.

Relationship between early-career collaboration among researchers and future funding success in Japanese academia.

Academia is becoming more and more competitive, especially for young scientists, so it is important to understand the factors that affect success in academic careers. To survive in academia, it is crucial to obtain research funding. Previous studies have investigated factors that affect the funding success of researchers.

Thyroidal Transcriptomic Profiles of Pathoadaptive Responses to Congenital Hypothyroidism in XB130 Knockout Mice.

Congenital hypothyroidism is a genetic condition in which the thyroid gland fails to produce sufficient thyroid hormone (TH), resulting in metabolic dysfunction and growth retardation. Xb130 mice exhibit perturbations of thyrocyte cytoskeleton and polarity, and develop postnatal transient growth retardation due to congenital hypothyroidism, leading ultimately to multinodular goiter. To determine the underlying mechanisms, we performed transcriptomic analyses on thyroid glands of mice at three age points: week 2 (W2, before visible growth retardation), W4 (at the nadir of growth); and W12 (immediately before full growth recovery).

Pathogenesis of Multinodular Goiter in Elderly XB130-Deficient Mice: Alteration of Thyroperoxidase Affinity with Iodide and Hydrogen Peroxide.

Multinodular goiter (MNG) is the most common disorder of the thyroid gland. Aging and genetic mutations that impair thyroid hormone (TH) production have been implicated in the development of MNG. XB130 is an adaptor/scaffold protein predominantly expressed in the thyroid gland.

Ischemia-Reperfusion Injury in a Simulated Lung Transplant Setting Differentially Regulates Transcriptomic Profiles between Human Lung Endothelial and Epithelial Cells.

Current understanding of mechanisms of ischemia-reperfusion-induced lung injury during lung preservation and transplantation is mainly based on clinical observations and animal studies. Herein, we used cell and systems biology approaches to explore these mechanisms at transcriptomics levels, especially by focusing on the differences between human lung endothelial and epithelial cells, which are crucial for maintaining essential lung structure and function. Human pulmonary microvascular endothelial cells and human lung epithelial cells were cultured to confluent, subjected to different cold ischemic times (CIT) to mimic static cold storage with preservation solution, and then subjected to warm reperfusion with a serum containing culture medium to simulate lung transplantation.

XB130 Plays an Essential Role in Folliculogenesis Through Mediating Interactions Between Microfilament and Microtubule Systems in Thyrocytes.

XB130 (actin filament-associated protein 1-like 2, AFAP1L2) is a thyroid-abundant adaptor/scaffold protein. mice exhibit transient growth retardation postnatally due to congenital hypothyroidism with diminished thyroglobulin iodination and release at both embryonic and early postnatal stages due to disorganized thyroid apical membrane structure and function. We hypothesized that XB130 is crucial for polarity and folliculogenesis by mediating proper cytoskeletal structure and function in thyrocytes.

[A case of polysplenia syndrome with annular pancreas and agenesis of the dorsal pancreas].

A 69-year-old woman had a history of acute pancreatitis. On abdominal computed tomography, the pancreatic body and tail could not be visualized, and the pancreatic head encircled the descending part of the duodenum. On endoscopic retrograde cholangiopancreatography, we could not find the minor papilla.

Arg302 governs the pK of Glu325 in LacY.

Lactose permease is a paradigm for the major facilitator superfamily, the largest family of ion-coupled membrane transport proteins known at present. LacY carries out the coupled stoichiometric symport of a galactoside with an H, using the free energy released from downhill translocation of H to drive accumulation of galactosides against a concentration gradient. In neutrophilic , internal pH is kept at ∼7.

A case of liver hilar tuberculous lymphadenitis complicated by biliary stricture diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

This report describes a case of liver hilar tuberculous lymphadenitis complicated by biliary stricture, diagnosed with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). A 44-year-old woman was referred to our center for further evaluation of abnormal liver function tests. Abdominal ultrasound/contrast-enhanced computed tomography (CT) revealed a 15-mm hypovascular mass with a weakly enhanced margin at the liver hilum.

Pentraxin 3 deficiency enhances features of chronic rejection in a mouse orthotopic lung transplantation model.

Chronic lung allograft dysfunction (CLAD) is a serious complication after lung transplantation and thought to represent chronic rejection. Increased expression of Pentraxin 3 (PTX3), an acute phase protein, was associated with worse outcome in lung transplant patients. To determine the role of recipient PTX3 in development of chronic rejection, we used a minor alloantigen-mismatched murine orthotopic single lung transplant model.

Genome-Wide Association Study Identifies TLL1 Variant Associated With Development of Hepatocellular Carcinoma After Eradication of Hepatitis C Virus Infection.

Background & Aims: There is still a risk for hepatocellular carcinoma (HCC) development after eradication of hepatitis C virus (HCV) infection with antiviral agents. We investigated genetic factors associated with the development of HCC in patients with a sustained virologic response (SVR) to treatment for chronic HCV infection.

Methods: We obtained genomic DNA from 457 patients in Japan with a SVR to interferon-based treatment for chronic HCV infection from 2007 through 2015.

pK of Glu325 in LacY.

Lactose permease (LacY), a paradigm for the largest family of membrane transport proteins, catalyzes the coupled translocation of a galactoside and a H across the cytoplasmic membrane of (galactoside/H symport). One of the most important aspects of the mechanism is the relationship between protonation and binding of the cargo galactopyranoside. In this regard, it has been shown that protonation is required for binding.

Late Reactivation of Hepatitis B Virus after Chemotherapies for Hematological Malignancies: A Case Report and Review of the Literature.

Reactivation of hepatitis B virus (HBV) is a serious complication of immunosuppressive therapy and cytotoxic chemotherapy. The optimal duration of HBV-DNA monitoring for at-risk patients depends on the clinical features of reactivation, especially the range of potency from therapies to reactivation. We present a case of very late reactivation after chemotherapy for lymphoma and review previous reports of late reactivation cases.

YidC assists the stepwise and stochastic folding of membrane proteins.

How chaperones, insertases and translocases facilitate insertion and folding of complex cytoplasmic proteins into cellular membranes is not fully understood. Here we utilize single-molecule force spectroscopy to observe YidC, a transmembrane chaperone and insertase, sculpting the folding trajectory of the polytopic α-helical membrane protein lactose permease (LacY). In the absence of YidC, unfolded LacY inserts individual structural segments into the membrane; however, misfolding dominates the process so that folding cannot be completed.

A case of a teenage boy with eosinophilic gastroenteritis with esophageal involvement developing a hemorrhagic duodenal ulcer.

A boy in his early teens visited our hospital with chief complaints of hematemesis and tarry stools. Upper gastrointestinal endoscopy identified a hemorrhagic duodenal ulcer, for which hemostasis was performed using a clip. Proton pump inhibitor (PPI) administration diminished the ulcer but relapse occurred after PPI discontinuation.

Observing a lipid-dependent alteration in single lactose permeases.

Lipids of the Escherichia coli membrane are mainly composed of 70%-80% phosphatidylethanolamine (PE) and 20%-25% phosphatidylglycerol (PG). Biochemical studies indicate that the depletion of PE causes inversion of the N-terminal helix bundle of the lactose permease (LacY), and helix VII becomes extramembranous. Here we study this phenomenon using single-molecule force spectroscopy, which is sensitive to the structure of membrane proteins.

Substrate-induced changes in the structural properties of LacY.

The lactose permease (LacY) of Escherichia coli, a paradigm for the major facilitator superfamily, catalyzes the coupled stoichiometric translocation of a galactopyranoside and an H(+) across the cytoplasmic membrane. To catalyze transport, LacY undergoes large conformational changes that allow alternating access of sugar- and H(+)-binding sites to either side of the membrane. Despite strong evidence for an alternating access mechanism, it remains unclear how H(+)- and sugar-binding trigger the cascade of interactions leading to alternating conformational states.

Trp replacements for tightly interacting Gly-Gly pairs in LacY stabilize an outward-facing conformation.

Trp replacements for conserved Gly-Gly pairs between the N- and C-terminal six-helix bundles on the periplasmic side of lactose permease (LacY) cause complete loss of transport activity with little or no effect on sugar binding. Moreover, the detergent-solubilized mutants exhibit much greater thermal stability than WT LacY. A Cys replacement for Asn245, which is inaccessible/unreactive in WT LacY, alkylates readily in the Gly→Trp mutants, indicating that the periplasmic cavity is patent.

Role of protons in sugar binding to LacY.

WT lactose permease of Escherichia coli (LacY) reconstituted into proteoliposomes loaded with a pH-sensitive fluorophore exhibits robust uphill H(+) translocation coupled with downhill lactose transport. However, galactoside binding by mutants defective in lactose-induced H(+) translocation is not accompanied by release of an H(+) on the interior of the proteoliposomes. Because the pK(a) value for galactoside binding is ∼10.

Dynamics of the L-fucose/H+ symporter revealed by fluorescence spectroscopy.

FucP of Escherichia coli catalyzes L-fucose/H(+) symport, and a crystal structure in an outward-facing conformation has been reported. However, nothing is known about FucP conformational dynamics. Here, we show that addition of L-fucose to purified FucP in detergent induces ∼20% quenching of Trp fluorescence in a concentration-dependent manner without a shift in λ(max).

[A case report of pancreatic serous cystadenoma coexistent with adenosquamous carcinoma].

A 70-year-old man was admitted to our hospital because a mass was incidentally found in the body of the pancreas. The mass was suspected to be serous cystadenoma from the findings of abdominal enhanced computed tomography, magnetic resonance imaging and endoscopic ultrasonography. In addition, another solid mass was detected in the pancreatic head on imaging tests.

Sugar recognition by CscB and LacY.

The sucrose permease (CscB) and lactose permease (LacY) of Escherichia coli belong to the oligosaccharide/H(+) symporter subfamily of the major facilitator superfamily, and both catalyze sugar/H(+) symport across the cytoplasmic membrane. Thus far, there is no common substrate for the two permeases; CscB transports sucrose, and LacY is highly specific for galactopyranosides. Determinants for CscB sugar specificity are unclear, but the structural organization of key residues involved in sugar binding appears to be similar in CscB and LacY.

Opening the periplasmic cavity in lactose permease is the limiting step for sugar binding.

The lactose permease (LacY) catalyzes galactoside/H(+) symport via an alternating access mechanism in which sugar- and H(+)-binding sites in the middle of the molecule are alternatively exposed to either side of the membrane by opening and closing of inward- and outward-facing cavities. The crystal structures of wild-type LacY, as well as accessibility data for the protein in the membrane, provide strong support for a conformation with a tightly closed periplasmic side and an open cytoplasmic side (an inward-facing conformation). In this study, rates of substrate binding were measured by stopped-flow with purified LacY either in detergent or in reconstituted proteoliposomes.