Tibial sided Anterolateral Ligament Injuries are Associated with Poor Healing and Residual Pivot Shift Testing Following Anterior Cruciate Ligament Reconstruction.

PURPOSE: ; to investigate if tibial sided anterolateral ligament (ALL) injuries are associated with poor healing and residual pivot shift. METHODS: ; Patients who underwent anterior cruciate ligament reconstructions within postinjury 6 weeks from January 2008 to March 2021 were included. They had concomitant ALL injury confirmed by preoperative magnetic resonance imaging (MRI) and were followed minimum 20 months. Preoperative ALL injury was graded by the Muramatsu classification and postoperative ALL healing were graded by a modification of the Lee classification (good, partial, and non-visualized). The patients were allocated to an improved group (IG) and an unimproved group (UG) based on a comparison of pre- and postoperative MRI. ALL tear site, postoperative knee stability, Lysholm score, and Tegner activity scale (PROs) were compared between the two groups. RESULTS: ; 128 patients were enrolled. 94.5 % patients achieved the minimal clinically important difference (MCID) for PROs, respectively. The ALL was torn at the femoral side in 46.9% patients, at mid-substance in 31.2.%, and at tibial side in 21.9%, Preoperatively, 86 (67.2%) patients had a partial tear and 42 (32.8%) patients had a complete tear. Based on the postoperative MRI appearances, 38 (29.7%) and 90 (70.3%) patients were allocated to the IG and UG, respectively. The tibial side tears were significantly frequent in UG (p= .032). Pivot shift showed a significantly higher incidence in UG than IG (p=.004). Lachman test and PROs did not differ between the two groups. CONCLUSIONS: ; Tibial-sided ALL tears occurred in 18.7% of the UG compared to 3.2% of the IG, and 45.6% of the UG had a postoperative grade 1 or 2 pivot shift, compared to 15.8% of the IG. Percentages of patients with the MCID for PROs did not differ between the two groups. However, the clinical relevance is limited by a high transfer bias.

Retrospective analysis on prognosis of oral cancer patients according to surgical approaches for effective cancer ablation: swing approach versus visor approach.

BACKGROUND: For the surgical treatment of oral cancer, it is sometimes necessary to expand intraoral access within the oral cavity. The "swing approach" that involves lip splitting of the mandible and temporary mandibular osteotomy and the "visor approach" that does not split the lower lip and mandible are mainly used. This study analyzed postoperative outcomes such as complications, recurrence rate, and survival rate by these two approaches. The goal of this study is to evaluate the surgical outcomes of patients using these two approaches, to propose effective perioperative management for oral cancer surgery, and to compare the prognosis of oral cancer patients. MATERIALS AND METHODS: From 2005 to 2020, 29 patients who underwent surgery at the Department of Oral and Maxillofacial Surgery of Pusan National University Dental Hospital for oral cancer lesions occurred in the mandible, floor of mouth, and tongue were selected for the study. Based on the surgical approach used, a chart review was conducted on various prognostic clinical factors such as the patients' sex and age, primary site, TNM stage, histopathologic grade, recurrence and metastasis, postoperative survival rate, adjuvant chemo-radiation therapy, satisfaction with aesthetics/function/swallowing, length of hospital stay, tracheostomy and its duration, and neck dissection and its type. Statistical analysis was conducted using SPSS 25.0 (SPSS Inc., Chicago, IL) through Fisher's exact t-test. RESULT: There was no statistically significant difference between two groups in terms of clinical and pathological findings, such as survival rate, the need for adjuvant therapies, and the local recurrence rate. Although better outcomes were observed in terms of function, aesthetics, and postoperative complications in the group with visor approach, there was still no statistically significant difference between two groups. However, the duration of hospital stay was shorter in the visor approach group. CONCLUSION: There was no statistically significant difference in clinical prognostic factors between the swing approach and the visor approach. Therefore, when choosing between the two approaches for the ablation of oral cancer, it is considered to select the surgical priority approach that can be easy access based on the size and location of the lesion. The visor approach had advantages of aesthetics and healing period.

Radio frequency hyperthermia system for skin tightening effect by filled waveguide aperture antenna with compact metamaterials.

Radio frequency (RF) hyperthermia focuses on raising the target area temperature to a value exceeding 45°C. Collagen is stimulated when the temperature rises to 45°C at the dermal layer, resulting in skin tightening. However, most studies on RF hyperthermia have focused on tumor ablation or using electrodes to radiate an electromagnetic field, which is highly inefficient. This study proposed a non-invasive RF hyperthermia skin-tightening system with a compact metamaterial-filled waveguide aperture antenna. The proposed RF system increased the temperature by 11.6°C and 35.3°C with 20 and 80 W of 2.45 GHz RF power, respectively, within 60 s and exhibited a very focused effective area. Furthermore, a metamaterial was proposed to reduce the size of the waveguide aperture antenna and focus the electromagnetic field in the near-field region. The proposed metamaterial-filled waveguide aperture antenna was compact, measuring 10 mm × 17.4 mm, with a peak gain of 2.2 dB at 2.45 GHz. The measured hyperthermia performance indicated that the proposed RF system exhibited better power- and time-efficient hyperthermia performance than other RF hyperthermia systems in the cosmetic skin lifting commercial market. The proposed RF hyperthermia systems will be applied into a new generation of beauty cosmetic devices.

Association of Increased Lateral Femoral Condylar Ratio With Lateral Meniscus Posterior Root Tear in Noncontact ACL Injury.

Background: In the setting of anterior cruciate ligament (ACL) injury, lateral meniscus posterior root tears (LMPRTs) are less readily diagnosed on preoperative magnetic resonance imaging (MRI). Therefore, to predict LMPRTs in ACL injuries, it is necessary to understand the risk factors associated with them. Purpose/Hypothesis: The purpose of this study was to investigate the association of lateral femoral condylar ratio (LFCR) with LMPRTs in ACL injuries. It was hypothesized that an increased LFCR would be associated with LMPRTs in noncontact ACL injuries. Study Design: Cohort study; Level of evidence, 3. Methods: Enrolled were consecutive patients who underwent primary acute (<6 weeks from injury) ACL reconstruction after noncontact injury and had LMPRT confirmed on preoperative MRI and arthroscopically (combined group; n = 62) as well as patients who underwent isolated acute ACL reconstruction (isolated group; n = 80) who were matched to the combined group by age, height, and body mass index (BMI). All patients underwent surgery between January 1999 and November 2021. LFCR and posterior tibial slope (PTS) were measured and compared between the isolated and combined groups. The area under the receiver operating characteristic curve (AUC) was calculated to determine the cutoff for detecting increased risk of LMPRTs. Results: The demographic characteristics of the 2 groups did not differ significantly, nor did the PTS. The LFCR was a significant factor (odds ratio [OR], 1.23; P = .001) associated with LMPRT. Patient age, height, BMI, and PTS were not associated with LMPRT. The AUC (0.66; 95% CI, 0.57-0.75) for LFCR had a sensitivity of 39% and specificity of 90% to predict LMPRT. The calculated cutoff associated with an increased risk for LMPRT when compared with the isolated group was 67.0% (OR, 4.98; 95% CI, 2.10-11.79). Conclusion: Increased LFCR was associated with the presence of LMPRTs in patients with acute ACL injuries. The LFCR may provide surgeons with additional information regarding the risk of having a concomitant LMPRT when planning ACL reconstructions.

A single-component, light-assisted uncaging switch for endoproteolytic release.

Proteases function as pivotal molecular switches, initiating numerous biological events. Notably, potyviral protease, derived from plant viruses, has emerged as a trusted proteolytic switch in synthetic biological circuits. To harness their capabilities, we have developed a single-component photocleavable switch, termed LAUNCHER (Light-Assisted UNcaging switCH for Endoproteolytic Release), by employing a circularly permutated tobacco etch virus protease and a blue-light-gated substrate, which are connected by fine-tuned intermodular linkers. As a single-component system, LAUNCHER exhibits a superior signal-to-noise ratio compared with multi-component systems, enabling precise and user-controllable release of payloads. This characteristic renders LAUNCHER highly suitable for diverse cellular applications, including transgene expression, tailored subcellular translocation and optochemogenetics. Additionally, the plug-and-play integration of LAUNCHER into existing synthetic circuits facilitates the enhancement of circuit performance. The demonstrated efficacy of LAUNCHER in improving existing circuitry underscores its significant potential for expanding its utilization in various applications.

Intravascular papillary endothelial hyperplasia in the lungs of a wild Korean raccoon dog.

A male Korean raccoon dog of unknown age was rescued and placed at the Daejeon Wildlife Rescue Center, Korea. Physical examination revealed severe emaciation and dehydration, as well as thick crusts and alopecia over most of the body. During medical care, the animal died and was submitted for postmortem examination. Firm, brown-red lesions of various sizes were observed on the surface of the lungs. In cross-sections of the lungs, pulmonary vessels were thickened and dilated, with white irregular papillary luminal projections. Histologically, pulmonary blood vessels were severely hyperplastic, characterized by thickened dilated walls and fibrous papillary projections covered with a single layer of endothelial cells (ECs). Hyperplastic fibrous connective tissue was confirmed by Masson trichrome staining. The ECs expressed CD31. We diagnosed the lesion as intravascular papillary endothelial hyperplasia, a unique non-neoplastic reactive process that has not been reported previously in pulmonary vessels of canids, equids, or felids, to our knowledge.

Bond Behavior of Steel Rebar Embedded in Cementitious Composites Containing Polyvinyl Alcohol (PVA) Fibers and Carbon Nanotubes (CNTs).

In this study, pull-out tests were conducted to investigate the bond behavior of a rebar embedded in cementitious composites with polyvinyl alcohol (PVA) fibers and carbon nanotubes (CNTs). In the cementitious composites, the binder consisted of ordinary Portland cement, blast furnace slag, and fly ash, with a weight ratio of 39.5, 21.0 and 39.5%, respectively, while the nonbinder consisted of quartzite sand, lightweight aggregate, superplasticizer, and shrinkage-reducing admixture. The water/binder ratio and volume fractions of the PVA fibers were 32.9% and 2.07%, respectively. In the test program, the rebar diameter (D13, D16, and D19) and CNTs mix ratio (0.0, 0.1, 0.2, and 0.3 wt.%) were considered as the test variables. The test results showed that the bond strength of a rebar increased as the rebar diameter decreased or as the CNTs mix ratio increased. Based on the test results, a new, simple model has been proposed with consideration of the rebar diameter, as well as the CNTs mix ratio. Comparing the test results, it was investigated that the proposed model generally represented the bond behavior well, including the bond strength and the corresponding slip of a rebar embedded in PVA cementitious composites, with or without CNTs.

Combined Anterolateral Ligament and Anterior Cruciate Ligament Injury Is Associated With Increased Lateral Femoral Condyle Ratio.

PURPOSE: to investigate the association between the lateral femoral condylar ratio (LFCR), the posterior tibial slope (PTS), and injury of the anterolateral ligament (ALL). METHODS: Inclusion criteria were patients with acute anterior cruciate ligament (ACL) tear after noncontact injury during sports from October 1997 to May 2021. The LFCR and PTS were measured, and injury of the ALL was evaluated. Patients were divided into 2 groups: isolated ACL tear (isolated group) and combined ACL with ALL tear (combined group). The LFCR and PTS were compared between the isolated and combined groups. For each risk factor, the receiver operating characteristic curve, the area under the curve (AUC), and its 95% confidence interval (CI) were calculated to determine the cutoff for detecting increased risk of ALL injury. RESULTS: There were 83 patients in the isolated group and 176 patients in the combined group. Demographics of the 2 groups did not differ significantly. The LFCR was significantly larger in the combined group than in the isolated group (P = .000). The PTS did not differ between the two groups (P = .405). The LFCR (odds ratio [OR] = 1.58; P = .000) was a significant factor. Age, body mass index, and PTS were not associated with an ALL injury. The AUC (0.79; 95% CI, 0.74-0.85) for the LFCR had a sensitivity of 73% and specificity of 76% to predict an ALL rupture. The calculated cutoff of 64.5 was associated with an increased risk for ALL rupture (OR = 8.65; 95% CI, 4.73-15.81) when compared with the isolated group. CONCLUSIONS: An increased LFCR was associated with the ALL injury. However, increased PTS was not associated with ALL injury. These findings need to be considered for clinicians in treating ACL tear patients at risk for an ALL injury. LEVEL OF EVIDENCE: III, retrospective comparative prognostic trial.

Correlation Between Anatomic Landmarks and Bony Trough Position in Lateral Meniscal Allograft Transplant.

Background: Determining the rotational axis of the bony trough during lateral meniscal allograft transplant (MAT) is difficult. The use of anatomic landmarks may help a surgeon determine the rotational alignment of the graft during the procedure. Purpose: To investigate the association between the knee's anatomic landmarks and the position of the bony trough to prevent extrusion after lateral MAT. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Enrolled were 44 patients who underwent lateral MAT between July 2000 and February 2011. The patients' mean age at the time of surgery was 30.8 years. Extrusion was measured on magnetic resonance imaging (MRI) scans at a mean of 3.6 months postoperatively, and patients were divided into an extrusion group (n = 15) and a no-extrusion group (n = 29). Three coronal MRI scans from each patient were selected, each from the region at the level of the tibial tuberosity (TT), the anterior bony trough, and the posterior bony trough. We measured the distance between the center of the anterior bony trough and the center of the TT (the TT distance) and the distance between the center of the posterior bony trough and the medial border of the lateral femoral condyle (LFC) (the LFC distance). Results: The mean center of the anterior bony trough was in a more medial position relative to the center of the TT in the no-extrusion group (-2.9 ± 4.8 mm) compared with the extrusion group (1.3 ± 4.9 mm; P = .010). The mean center of the posterior bony trough was in a more medial position relative to the medial border of the LFC in the no-extrusion group (-1.7 ± 3.9 mm) compared with the extrusion group (1.0 ± 3.2 mm; P = .027). Both TT distance and LFC distance were significantly correlated with extrusion (P = .005 and .025, respectively). The cutoff value was -0.24 mm for the anterior bony trough and -0.58 mm for the posterior bony trough (negative values indicate that the trough was medial to the respective landmarks). Conclusion: To prevent extrusion of the allograft, the center of the anterior bony trough needs to be aligned with the center of the TT, and the center of the posterior bony trough needs to be aligned with the medial border of the LFC.

PSMD14 Targeting Triggers Paraptosis in Breast Cancer Cells by Inducing Proteasome Inhibition and Ca2+ Imbalance.

PSMD14, a subunit of the 19S regulatory particles of the 26S proteasome, was recently identified as a potential prognostic marker and therapeutic target in diverse human cancers. Here, we show that the silencing and pharmacological blockade of PSMD14 in MDA-MB 435S breast cancer cells induce paraptosis, a non-apoptotic cell death mode characterized by extensive vacuolation derived from the endoplasmic reticulum (ER) and mitochondria. The PSMD14 inhibitor, capzimin (CZM), inhibits proteasome activity but differs from the 20S proteasome subunit-inhibiting bortezomib (Bz) in that it does not induce aggresome formation or Nrf1 upregulation, which underlie Bz resistance in cancer cells. In addition to proteasome inhibition, the release of Ca2+ from the ER into the cytosol critically contributes to CZM-induced paraptosis. Induction of paraptosis by targeting PSMD14 may provide an attractive therapeutic strategy against cancer cells resistant to proteasome inhibitors or pro-apoptotic drugs.

Genotypes of Echinococcus Species from Cattle in Tanzania.

Cystic echinococcosis is a zoonotic parasitic disease caused by Echinococcus species. Tanzania is one of the endemic countries with cystic echinococcosis. This study focussed on identifying genotypes of Echinococcus spp. in Tanzania. We collected 7 cysts from cattle in Mwanza municipal (n=4) and Loliondo district (n=3). The cysts from Mwanza were all E. ortleppi and fertile. In contrast, the cysts from Loliondo were all E. granulosus sensu stricto and sterile. Two from the 4 cysts were a new haplotype of E. ortleppi (G5). These results can improve the preventive and control programs for humans and livestock in Tanzania. To our knowledge, this study is considered the first to identify the genotype and haplotype of Echinococcus spp. in Tanzania.

Trifunctional layered electrodeposited nickel iron hydroxide electrocatalyst with enhanced performance towards the oxidation of water, urea and hydrazine.

In recent years, low-cost, non-noble metal-based and stable catalysts have gained attention for the development of clean energy devices. Additionally, the synthesis of materials that can exhibit more than one electrocatalytic reaction is notable. In this work, stepwise electrodeposited nickel-iron hydroxide nanoarrays are investigated as anode electrocatalysts with enhanced performance towards the oxidation of water, urea, and hydrazine. The stepwise electrodeposited nickel-iron hydroxide (NiFe(OH)2-SD/NF) electrodes show excellent electrocatalytic activity and stability for the oxygen evolution reaction (OER) with a low potential of 1.45 V (vs RHE) at a current density of 10 mA cm-2. These electrodes further display excellent catalytic activity towards the urea oxidation reaction (UOR) and hydrazine oxidation reaction (HzOR) with potentials lower than 1.32 V (vs RHE) and 0.06 V (vs RHE), respectively. Owing to synergistic effects, a porous structure for mass transport leads to excellent electrocatalytic performance. This non-precious-metal nickel-iron hydroxide, prepared by a simple synthesis approach, is promising for hybrid water electrolysis applications and the development of environmentally friendly clean energy reactions.

A Clonorchiasis Case of a Leopard Cat, Prionailurus bengalensis euptilurus, Diagnosed by Ultrasonography and Egg Detection in Republic of Korea.

A clonorchiasis case in a captive leopard cat, Prionailurus bengalensis euptilurus, was confirmed by ultrasonographic findings and egg morphologies found in the bile juice sample in the Korea. The leopard cat was introduced from the wild habitat of Gyeongsangnam-do, to Cheongju Zoo in Cheongju-si, Chungcheongbuk-do, Korea in August 2014. Physical examinations were basically performed for quarantine and check-up health. The cat was comparatively good in health except anorexia. The cyst-like bile duct dilation and the increased echogenicity of gall bladder wall and hepatic parenchyma were observed by ultrasonography. Ultrasound-guided needle biopsy was conducted for collecting bile juice and the specimens were observed under light microscope. The numerous small trematode eggs were detected in the bile juice sample of the light microscopy. The eggs were 25-33 (28±3) µm by 18-22 (20±1) µm in size and showed typical characteristics of Clonorchis sinensis egg, i.e., a dominantly developed operculum, shoulder rim and dust-like wrinkles in surface. To treat the liver fluke infection, 20 mg/kg of praziquantel was orally administered only once to the case. Follow-up studies including fecal examinations were conducted during 2 years after treatment. But no more eggs were detected from the case. In the present study, we described the first clonorchiasis case of leopard cat, which was confirmed by ultrasonographic findings and egg morphologies from the bile juice sample in Korea.

Echinostoma macrorchis Metacercariae in Cipangopaludina chinensis malleata from Xiengkhuang Province, Lao PDR and Morphologies of Adults from Experimental Animals.

We identified the echinostome metacercariae in Chinese mystery snails, Cipangopaludina chinensis malleata, from Xiengkhuang Province, Lao PDR with morphologies of adult worms recovered. Total 20 snails were examined with artificial digestion method and then the collected metacercariae were orally infected to a mouse and a rat. Adult worms recovered from experimental animals were observed with a light microscope and a SEM. The metacercariae were round, 125×123 µm in average size, with a moderately thick cyst wall, collar spines distributed in the head collar and excretory granules in 2 canals of excretory tube. Adult flukes (3-week-old in a rat) were elongated, ventrally curved and 5.310×1.023 mm in average size. Head collar distinct, bearing 43 collar spines with 5 end group ones on each side. Oral sucker subterminal, prepharynx very short, pharynx well developed, and esophagus relatively short. Cirrus sac well developed, with a saccular seminal vesicle, and ventral sucker very large. Ovary round and on the median line of the body. Testes tandom and elongated. Eggs operculated, elliptical and 90×57 µm in average size. In the SEM observation, the head crown prominent, with 43 collar spines resembled with horns of younger stag. Scale-like tegumental spines were densely distributed on the surface between the head collar and ventral sucker, and their densities were decreased posteriorly. Conclusively, the metacercariae detected in C. chinensis malleata from Lao PDR were identified as those of Echinostoma macrorchis based on the morphological characteristics of adult worms.

PKA-dependent phosphorylation of IP3K-A at Ser119 regulates a binding affinity with EB3.

Microtubule-associated end-binding protein 3 (EB3) accumulates asymmetrically at the tip-end of growing microtubules, providing a central platform for linking various cellular components. EB3 orchestrates microtubule dynamics and targeting, enabling diverse processes within neurons. Inositol 1, 4, 5-trisphosphate 3-kinase A (IP3K-A; also known as ITPKA) is a neuron-enriched protein that binds to microtubules by PKA-dependent manners. In this study, we found that IP3K-A binds to EB3 and their binding affinity is precisely regulated by protein kinase A (PKA)-dependent phosphorylation of IP3K-A at Ser119 (pSer119). We also revealed that the complex of IP3K-A and EB3 dissociates and reassociates rapidly during chemically induced LTP (cLTP) condition. This dynamic rearrangement of IP3K-A and EB3 complex will contribute remodeling of microtubule cytoskeleton allowing effective structural plasticity in response to synaptic stimulations.

Temporally precise labeling and control of neuromodulatory circuits in the mammalian brain.

Few tools exist to visualize and manipulate neurons that are targets of neuromodulators. We present iTango, a light- and ligand-gated gene expression system based on a light-inducible split tobacco etch virus protease. Cells expressing the iTango system exhibit increased expression of a marker gene in the presence of dopamine and blue-light exposure, both in vitro and in vivo. We demonstrated the iTango system in a behaviorally relevant context, by inducing expression of optogenetic tools in neurons under dopaminergic control during a behavior of interest. We thereby gained optogenetic control of these behaviorally relevant neurons. We applied the iTango system to decipher the roles of two classes of dopaminergic neurons in the mouse nucleus accumbens in a sensitized locomotor response to cocaine. Thus, the iTango platform allows for control of neuromodulatory circuits in a genetically and functionally defined manner with spatial and temporal precision.

A Case of Chaunocephalosis by Chaunocephalus ferox (Digenea: Echinostomatidae) in an Oriental White Stork, Ciconia boyciana, in Korea.

We intended to describe a case of chaunocephalosis and morphological characteristics of its causative agent, Chaunocephalus ferox, recovered from an oriental white stork, Ciconia boyciana, in the Republic of Korea. An oriental white stork was referred to the Wildlife Center of Chungbuk in Korea in February 2014 for severe depression with cachexia and it died the next day. At necropsy, the stomach was severely expanded and 7 thick-walled nodules were observed in the upper part of the intestine. Although the stomach was filled with full of foreign materials, the intestine was almost empty. The nodules were globular and total 9 flukes were recovered. They were 8,030-8,091 µm in length and 3,318-3,333 µm in maximum width. Because the flukes had bulbous forebody with short narrow subcylindrical hindbody, 27 collar spines, and vitelline follicles not reaching to the posterior end, the specimens were identified as being C. ferox. The cyst formation induced thickening of the intestinal wall with narrowing of the lumen that could have contributed to the gastric impaction to the death of the host. This is the first described case of chaunocephalosis and its causative agent C. ferox found from an oriental white stork in Korea.

Early growth response 1 (Egr-1) directly regulates GABAA receptor α2, α4, and θ subunits in the hippocampus.

The homeostatic regulation of neuronal activity in glutamatergic and GABAergic synapses is critical for neural circuit development and synaptic plasticity. The induced expression of the transcription factor early growth response 1 (Egr-1) in neurons is tightly associated with many forms of neuronal activity, but the underlying target genes in the brain remained to be elucidated. This study uses a quantitative real-time PCR approach, in combination with in vivo chromatin immunoprecipitation, and reveals that GABAA receptor subunit, GABRA2 (α2), GABRA4 (α4), and GABRQ (θ) genes, are transcriptional targets of Egr-1. Transfection of a construct that over-expresses Egr-1 in neuroblastoma (Neuro2A) cells up-regulates the α2, α4, and θ subunits. Given that Egr-1 knockout mice display less GABRA2, GABRA4, and GRBRQ mRNA in the hippocampus, and that Egr-1 directly binds to their promoters and induces mRNA expression, the present findings support a role for Egr-1 as a major regulator for altered GABAA receptor composition in homeostatic plasticity, in a glutamatergic activity-dependent manner. The early growth response 1 (Egr-1) is an inducible transcription factor to mediate rapid gene expression by neuronal activity. However, its underlying molecular target genes and mechanisms are not fully understood. We suggest that GABAA receptor subunits, GABRA2 (α2), GABRA4 (α4), and GABRQ (θ) genes are transcriptional targets of Egr-1. Neuronal activity-dependent up-regulation of Egr-1 might lead to altered subtypes of GABAA receptors for the maintenance of homeostatic excitatory and inhibitory balance for the regulation of synaptic strength.

SDS3 interacts with ARNT in an AhR ligand-specific manner regulating expression of cKrox and S100A4 in CD4+CD8+ DPK thymocytes differentiation.

To study mechanisms underlying differential effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and benzo(a)pyrene (B(a)P) on thymocyte differentiation, we examined effects of AhR ligands on the differentiation of DPK cells, a CD4(+)CD8(+) thymic lymphoma cell line which can differentiate into CD4(+)CD8(-) thymocytes. In contrast to TCDD, which inhibited the differentiation, B(a)P showed little effect. Antigen-mediated up-regulation of S100A4, S100A6, galectin-1, and TRAF5-like protein was remarkably suppressed by TCDD, but slightly by B(a)P. Immunoprecipitation using anti-ARNT Ab revealed that SDS3, a component of the Sin3/HDAC repressor complex, was associated with ARNT only when DPK cells were incubated with TCDD. Expression of cKrox S100A4 was derepressed when SDS3 protein was reduced. These results indicate that although it is generally known that many AhR ligands such as TCDD and B(a)P function mainly by the AhR/ARNT complex, ligand-specific interaction between SDS3 and ARNT exerts differential effects on the expression of genes associated with thymocyte differentiation.

Inositol 1,4,5-trisphosphate 3-kinase A is a novel microtubule-associated protein: PKA-dependent phosphoregulation of microtubule binding affinity.

Inositol 1,4,5-trisphosphate 3-kinase A (IP(3)K-A) is a brain specific and F-actin-binding protein. We recently demonstrated that IP(3)K-A modulates a structural reorganization of dendritic spines through F-actin remodeling, which is required for synaptic plasticity and memory formation in brain. However, detailed functions of IP(3)K-A and its regulatory mechanisms involved in the neuronal cytoskeletal dynamics still remain unknown. In the present study, we identified tubulin as a candidate of IP(3)K-A-binding protein through proteomic screening. By various in vitro and in vivo approaches, we demonstrated that IP(3)K-A was a novel microtubule-associated protein (MAP), and the N terminus of IP(3)K-A was a critical region for direct binding to tubulin in dendritic shaft of hippocampal neurons. Moreover, PKA phosphorylated Ser-119 within IP(3)K-A, leading to a significant reduction of microtubule binding affinity. These results suggest that PKA-dependent phosphorylation and microtubule binding of IP(3)K-A are involved in its regulatory mechanism for activity-dependent neuronal events such as local calcium signaling and its synaptic targeting.