Neural Systems Underlying the Implementation of Working Memory Removal Operations.

Recently, multi-voxel pattern analysis has verified that information can be removed from working memory (WM) via three distinct operations replacement, suppression, or clearing compared to information being maintained ( Kim et al., 2020). While univariate analyses and classifier importance maps in Kim et al. (2020) identified brain regions that contribute to these operations, they did not elucidate whether these regions represent the operations similarly or uniquely. Using Leiden-community-detection on a sample of 55 humans (17 male), we identified four brain networks, each of which has a unique configuration of multi-voxel activity patterns by which it represents these WM operations. The visual network (VN) shows similar multi-voxel patterns for maintain and replace, which are highly dissimilar from suppress and clear, suggesting this network differentiates whether an item is held in WM or not. The somatomotor network (SMN) shows a distinct multi-voxel pattern for clear relative to the other operations, indicating the uniqueness of this operation. The default mode network (DMN) has distinct patterns for suppress and clear, but these two operations are more similar to each other than to maintain and replace, a pattern intermediate to that of the VN and SMN. The frontoparietal control network (FPCN) displays distinct multi-voxel patterns for each of the four operations, suggesting that this network likely plays an important role in implementing these WM operations. These results indicate that the operations involved in removing information from WM can be performed in parallel by distinct brain networks, each of which has a particular configuration by which they represent these operations.

Suppressing the Maintenance of Information in Working Memory Alters Long-term Memory Traces.

The sensory recruitment hypothesis conceptualizes information in working memory as being activated representations of information in long-term memory. Accordingly, changes made to an item in working memory would be expected to influence its subsequent retention. Here, we tested the hypothesis that suppressing information from working memory, which can reduce short-term access to that information, may also alter its long-term neural representation. We obtained fMRI data (n = 25; 13 female / 12 male participants) while participants completed a working memory removal task with scene images as stimuli, followed by a final surprise recognition test of the examined items. We applied a multivariate pattern analysis to the data to quantify the engagement of suppression on each trial, to track the contents of working memory during suppression, and to assess representational changes afterward. Our analysis confirms previous reports that suppression of information in working memory involves focused attention to target and remove unwanted information. Furthermore, our findings provide new evidence that even a single dose of suppression of an item in working memory can (if engaged with sufficient strength) produce lasting changes in its neural representation, particularly weakening the unique, item-specific features, which leads to forgetting. Our study sheds light on the underlying mechanisms that contribute to the suppression of unwanted thoughts and highlights the dynamic interplay between working memory and long-term memory.

OsLRR-RLP2 Gene Regulates Immunity to Magnaporthe oryzae in Japonica Rice.

Rice is an important cereal crop worldwide, the growth of which is affected by rice blast disease, caused by the fungal pathogen Magnaporthe oryzae. As climate change increases the diversity of pathogens, the disease resistance genes (R genes) in plants must be identified. The major blast-resistance genes have been identified in indica rice varieties; therefore, japonica rice varieties with R genes now need to be identified. Because leucine-rich repeat (LRR) domain proteins possess R-gene properties, we used bioinformatics analysis to identify the rice candidate LRR domain receptor-like proteins (OsLRR-RLPs). OsLRR-RLP2, which contains six LRR domains, showed differences in the DNA sequence, containing 43 single-nucleotide polymorphisms (SNPs) in indica and japonica subpopulations. The results of the M. oryzae inoculation analysis indicated that indica varieties with partial deletion of OsLRR-RLP2 showed susceptibility, whereas japonica varieties with intact OsLRR-RLP2 showed resistance. The oslrr-rlp2 mutant, generated using clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), showed increased pathogen susceptibility, whereas plants overexpressing this gene showed pathogen resistance. These results indicate that OsLRR-RLP2 confers resistance to rice, and OsLRR-RLP2 may be useful for breeding resistant cultivars.

The Angular Gyrus as a Hub for Modulation of Language-related Cortex by Distinct Prefrontal Executive Control Regions.

It has become clear in recent years that reading, while relying on domain-specific language processing regions, also involves regions that implement executive processes more broadly. Such executive control is generally considered to be implemented by prefrontal regions, which exert control via connectivity that allows them to modulate processing in target brain regions. The present study examined whether three previously identified and distinct executive control regions in the pFC [Wang, K., Banich, M. T., Reineberg, A. E., Leopold, D. R., Willcutt, E. G., Cutting, L. E., et al. Left posterior prefrontal regions support domain-general executive processes needed for both reading and math. Journal of Neuropsychology, 14, 467-495, 2020] show similar patterns of functional connectivity (FC) during a reading comprehension task as compared with a symbol identification condition. Our FC results in a sample of adolescents (n = 120) suggest all three regions commonly show associations with activity in "classic" left hemisphere reading areas, including the angular and supramarginal gyri, yet each exhibits differential connectivity as well. In particular, precentral regions show differential FC to parietal portions of the dorsal language stream, the inferior frontal junction shows differential FC to middle temporal regions of the right hemisphere and other regions involved in semantic processing, and portions of the inferior frontal gyrus show differential FC to an extensive set of right hemisphere prefrontal regions. These results suggest that prefrontal control over language-related regions occurs in a coordinated yet discrete manner.

Health attacks and protection strategies during Gaza's Great March of Return: a mixed methods study using data from WHO's Surveillance System for Attacks on Healthcare.

BACKGROUND: WHO defines an attack on health care as "any act of verbal or physical violence or obstruction or threat of violence that interferes with the availability, access and delivery of curative and/or preventive health services during emergencies." Gaza's Great March of Return (GMR) began on Mar 30, 2018, with 322 Palestinians killed and 33 141 injured by December, 2019, and first-response health-care teams exposed to high levels of violence. The aims of this study were threefold: to explore the vulnerabilities of health workers to attacks during the GMR; to understand the effectiveness and comprehensiveness of systems for monitoring health attacks; and to identify potential strategies and interventions to improve protection. METHODS: WHO's Surveillance System for Attacks on Healthcare (SSA) verifies and records health attacks. We analysed SSA data for the Gaza Strip from Mar 30, 2018, to Dec 31, 2019, examining the number and type of attacks, the mechanisms of injury, and the distribution of attacks by gender, time, and location. We analysed the correlation of health worker injuries and deaths with total injuries and deaths of Palestinians during the GMR. We held interviews and focus groups with individuals working for organizations defined as partners contributing to the SSA in the Gaza Strip, to understand data comprehensiveness, the nature and impact of violence, and protection gaps and strategies. FINDINGS: During the study period, there were 567 confirmed incidents, in which three health workers were killed, 845 health workers were injured, and 129 ambulances and vehicles and 7 health facilities were damaged, including one hospital and three medical field stations. Of the total health personnel killed and injured, 166 of 848 (20%) were in the Gaza governorate, 274 (32%) were in the Khan Yunis governorate, 119 (14%) were in the middle governorate, 192 (22%) were in North governorate, and 96 (11%) were in the Rafah governorate. Of 845 injuries, 743 (88%) were in men, 45 (5%) were live ammunition injuries, 62 (7%) were rubber bullet injuries, 151 (18%) were gas canister injuries, 41 (5%) were shrapnel injuries, and 533 (64%) were gas inhalation injuries. Injuries and deaths among health workers correlated moderately (R2=0·54) with and accounted for 2% of the total. Qualitative findings highlighted the incidental and structural nature of violence, normalisation and under-reporting of attacks, the need for improved coordination of protection for health care, and gaps in the availability of protective equipment. INTERPRETATION: Health-care workers function at great personal risk. The correlation of attacks against health care with total injuries and deaths points to the need for alignment of efforts to protect health care with strategies to safeguard civilian populations, including protection of populations living under occupation and those engaged in civil demonstrations. Health-care workers identified the need for systemic measures to improve protection through training, monitoring, and coordination, and through linking of monitoring and documentation of health attacks with stronger accountability measures for prevention. FUNDING: In 2017 and 2018, WHO's Right to Health Advocacy programme received funding from the Swiss Development Cooperation and the oPt Humanitarian Fund.

Intramedullary parasite eggs, latent for three decades, mimicking acute transverse myelitis.

BACKGROUND: Intramedullary parasitic infection is extremely uncommon, and clinical presentation of Brown-Sequard syndrome is even rarer. CASE PRESENTATION: The authors report a case involving a 57-year-old woman with Brown-Sequard syndrome, in whom magnetic resonance imaging and clinical and epidemiological features were similar to those of acute transverse myelitis. Myelotomy suggested inflammation caused by latent parasite eggs in the spinal cord. Antiparasitic and steroid therapies were administered postoperatively. To the author's knowledge, this is the first report to describe a surgical experience for Taenia solium eggs in the spinal cord. CONCLUSION: Intramedullary parasitic infection is a diagnostic challenge that requires careful discrimination from other diseases. If parasite infection is suspected in a progressively deteriorating patient, myelotomy should be considered for rapid and accurate treatment.

Complementary Regulation of BfmRS Two-Component and AbaIR Quorum Sensing Systems to Express Virulence-Associated Genes in Acinetobacter baumannii.

Acinetobacter baumannii expresses various virulence factors to adapt to hostile environments and infect susceptible hosts. This study investigated the regulatory network of the BfmRS two-component and AbaIR quorum sensing (QS) systems in the expression of virulence-associated genes in A. baumannii ATCC 17978. The ΔbfmS mutant exhibited a significant decrease in surface motility, which presumably resulted from the low expression of pilT and A1S_0112-A1S_0119 gene cluster. The ΔbfmR mutant displayed a significant reduction in biofilm and pellicle formation due to the low expression of csu operon. The deletion of abaR did not affect the expression of bfmR or bfmS. However, the expression of abaR and abaI was upregulated in the ΔbfmR mutant. The ΔbfmR mutant also produced more autoinducers than did the wild-type strain, suggesting that BfmR negatively regulates the AbaIR QS system. The ΔbfmS mutant exhibited no autoinducer production in the bioassay system. The expression of the A1S_0112-A1S_0119 gene cluster was downregulated in the ΔabaR mutant, whereas the expression of csu operon was upregulated in this mutant with a high cell density. In conclusion, for the first time, we demonstrated that the BfmRS-AbaIR QS system axis regulated the expression of virulence-associated genes in A. baumannii. This study provides new insights into the complex network system involved in the regulation of virulence-associated genes underlying the pathogenicity of A. baumannii.

Prognostic value of metabolic activity of the psoas muscle evaluated by preoperative 18F-FDG PET-CT in breast cancer: a retrospective cross-sectional study.

BACKGROUND: This study aimed to evaluate the potential of metabolic activity of the psoas muscle measured by 18F-fluorodeoxyglucose positron emission tomography-computed tomography to predict treatment outcomes in patients with resectable breast cancer. METHODS: The medical records of 288 patients who had undergone surgical resection for stages I-III invasive ductal carcinoma of the breast between January 2014 and December 2014 in Pusan National University Hospital were reviewed. The standardized uptake values (SUVs) of the bilateral psoas muscle were normalized using the mean SUV of the liver. SUVRmax was calculated as the ratio of the maximum SUV of the average bilateral psoas muscle to the mean SUV of the liver. SUVRmean was calculated as the ratio of the mean SUV of the bilateral psoas muscle to the mean SUV of the liver. RESULTS: Univariate analyses identified a higher T stage, higher N stage, estrogen receptor negativity, progesterone receptor negativity, human epidermal growth factor receptor 2 positivity, triple-negative breast cancer, mastectomy (rather than breast-conserving surgery), SUVRmean > 0.464, and SUVRmax > 0.565 as significant adverse factors for disease-free survival (DFS). Multivariate Cox regression analysis revealed that N3 stage (hazard ratio [HR] = 5.347, P = 0.031) was an independent factor for recurrence. An SUVRmax > 0.565 (HR = 4.987, P = 0.050) seemed to have a correlation with shorter DFS. CONCLUSIONS: A higher SUVRmax of the psoas muscle, which could be a surrogate marker of insulin resistance, showed strong potential as an independent prognostic factor for recurrence in patients with resectable breast cancer.

Predictability Changes What We Remember in Familiar Temporal Contexts.

The human brain constantly anticipates the future based on memories of the past. Encountering a familiar situation reactivates memory of previous encounters, which can trigger a prediction of what comes next to facilitate responsiveness. However, a prediction error can lead to pruning of the offending memory, a process that weakens its representation in the brain and leads to forgetting. Our goal in this study was to evaluate whether memories are spared from such pruning in situations that allow for accurate predictions at the categorical level, despite prediction errors at the item level. Participants viewed a sequence of objects, some of which reappeared multiple times ("cues"), followed always by novel items. Half of the cues were followed by new items from different (unpredictable) categories, while others were followed by new items from a single (predictable) category. Pattern classification of fMRI data was used to identify category-specific predictions after each cue. Pruning was observed only in unpredictable contexts, while encoding of new items was less robust in predictable contexts. These findings demonstrate that how associative memories are updated is influenced by the reliability of abstract-level predictions in familiar contexts.

The feasibility of quantitative parameters of lymphoscintigraphy without significant dermal backflow for the evaluation of lymphedema in post-operative patients with breast cancer.

PURPOSE: We aimed to evaluate the potential role of quantitative methods associated with lymphoscintigraphy for the assessment of severity of lymphedema post-operatively in patients with breast cancer who did not show definite dermal backflow activity on the lymphoscintigraphy. METHODS: We evaluated 47 lymphoscintigraphies without dermal backflow in patients with lymphedema who received a mastectomy and axillary dissection or sentinel lymph node dissection for invasive ductal carcinoma of the breast. The quantitative asymmetry indices (QAIs) of both arms were calculated for each axilla, upper arm, forearm, and the whole arm. The QAI was defined as the radiopharmaceutical uptake ratio of the affected side to the unaffected side. Arm circumference was measured at four locations per arm to identify the maximal circumference difference (MCD) between affected and unaffected sides. RESULTS: The total and forearm QAIs of each side arm were significantly higher in the group with above moderate stage lymphedema compared with the mild stage group. Previous radiotherapy also had a significant effect on radiotracer retention expressed as QAI. The MCD was significantly correlated with QAI values of the forearm and the whole arm. The QAI of axillary areas was not significantly correlated with circumferential measurements of the arm. CONCLUSIONS: The QAIs have significant value for the diagnosis and severity of lymphedema and may therefore potentially be used as an objective tool for the assessment of lymphedema.

Gender differences exist in rotational anatomy of the distal femur in osteoarthritic knees using MRI.

PURPOSE: Optimal rotational alignment of the femoral component is essential for total knee arthroplasty (TKA). The femoral transepicondylar axis (TEA), Whiteside's line (WSL), and posterior condylar axis (PCA) are various intra-operative references that can be used to determine femoral rotation, and each has advantages and disadvantages. This study aimed to define the rotational anatomy of the distal femur and investigate its relationship with gender in osteoarthritic knees. METHODS: Magnetic resonance imaging (MRI) was obtained from 1522 patients (1298 females and 224 males) with end-stage knee osteoarthritis prior to TKA. MRI was constructed into three-dimensional models. The angles between the TEA and WSL, WSL and PCA, and TEA and PCA were calculated for each patient. In addition, gender differences in femoral rotation were evaluated. RESULTS: The PCA was 2.2° ± 1.0° internally rotated relative to the TEA. WSL was 1.2° ± 2.8° externally rotated relative to the TEA. The WSL to TEA relationship exhibited greater variability than the PCA to TEA relationship. PCA was more internally rotated and WSL was more externally rotated relative to TEA in female group than male group. Based on the standard reference rules of 3° external rotation from the PCA that has been conventionally used, 15.7% of patients showed external rotation lower 1° or greater than 5° external rotation from the PCA. In the mean external rotation of the TEA from the PCA (2.2°) from this population; however, the percentage of patients showing ± 2° from their TEA dropped to 5.1% of patients. CONCLUSION: Gender difference and variability exist in distal femoral rotational anatomy. These data can be useful in consideration of femoral anatomy variability and gender difference. The same cutting angle may lead to malrotation of the femoral component. LEVEL OF EVIDENCE: Consecutive patients, level III.

Anatomy-mimetic design preserves natural kinematics of knee joint in patient-specific mobile-bearing unicompartmental knee arthroplasty.

PURPOSE: This study aims to evaluate whether different tibial-femoral conformities for patient-specific mobile-bearing unicompartmental knee arthroplasties (UKAs) preserve natural knee kinematics, using computational simulations. METHODS: Different designs for patient-specific mobile-bearing UKAs were evaluated using finite element analysis. Three designs for the identical femoral component were considered: flat (non-conforming design), anatomy-mimetic, and conforming for the tibial insert. RESULTS: The conforming design for the patient-specific mobile-bearing UKAs exhibited a 1.2 mm and 0.7° decrease in the translation and rotation, respectively, in the swing phase compared with those of the natural knee. In addition, the femoral rollback and internal rotation were 2.6 mm and 1.2° lower, respectively, than those of the natural knee, for the conforming design under the deep-knee-bend condition. The flat design for the patient-specific mobile-bearing UKAs exhibited a 2.2 mm and 1.4° increase in the femoral rollback and rotation compared with the natural knee under the deep-knee-bend condition. The anatomy-mimetic patient-specific mobile-bearing UKAs best preserved the natural knee kinematics under the gait and deep-knee-bend loading conditions. CONCLUSIONS: The kinematics of the loading conditions in patient-specific mobile-bearing UKAs was determined to closely resemble those of a native knee. In additional, by replacing the anatomy-mimetic design with a mobile-bearing, natural knee kinematics during gait and deep-knee-bend motions is preserved. These results confirm the importance of tibiofemoral conformity in preserving native knee kinematics in patient-specific mobile-bearing UKA.

Gender difference exists in sagittal curvature of the distal femoral condyle morphology for osteoarthritic population.

PURPOSE: The aim of this study was to investigate gender-related differences in the sagittal curvature of the distal femoral condyle in the Korean osteoarthritic population METHODS: The sagittal curvatures of the distal femoral condyle of 1979 Korean patients (1680 female and 299 male) were evaluated using magnetic resonance imaging (MRI). MRI scans were obtained before total knee arthroplasty (TKA) in consecutive patients with end-stage osteoarthritis. The sagittal curvature of the distal medial and lateral femoral condyles was characterized with respect to the anterior, distal, and posterior circles. The diameter of each circle was measured. This study included 1873 varus and 106 valgus knees. RESULTS: The anterior, distal, and posterior diameters were significantly greater in the male patients than in the female patients (P < 0.05). In the male patients, the lateral diameter was significantly greater than the medial diameter in the anterior and posterior circles (P < 0.05). However, in the female patients, the lateral diameter was significantly greater only in the anterior circle. In both genders, the medial diameter was significantly greater than the lateral diameter of the distal circle (P < 0.05). For both the varus and valgus knees, the lateral diameter was greater than the medial diameter in the anterior circle. CONCLUSIONS: It has been concluded that the sagittal curvature of the femoral condyles in females is significantly different to their male counterparts. This study provides a reliable evaluation of the sagittal curvature of the femoral condyle in the Korean population. These gender-related differences in the sagittal curvature of the femoral condyle may require further investigation to determine surgical implications such as in TKA, and the existence of gender-related dimorphism in specific knee injuries and pathologies, such as ligament injuries and tibiofemoral problems. LEVEL OF EVIDENCE: III.

Residue Monitoring and Risk Assessment of Cyazofamid and Its Metabolite in Korean Cabbage Under Greenhouse Conditions.

The residual characteristics and risk assessment with respect to cyazofamid and its metabolite 4-chloro-5-p-tolylimidazole-2-carbonitrile were monitored in case of Korean cabbage at different preharvest intervals during a greenhouse trial. The 0.02 kg a.i/ha of cyazofamid was sprayed twice on seven-day intervals (i.e., on day 0, 7, 14, and 21 before harvest). The liquid chromatography-tandem mass spectrometry analysis was used to monitor the residual amount of fungicide. The matrix-matched calibration curves with respect to the cyazofamid in Korean cabbage exhibited good linearity (R2 ≥ 0.999) and acceptable recoveries of 84.1%-114.9%. The biological half-life of cyazofamid in Korean cabbage was 3.18 days. During the treatment, the preharvest residue of cyazofamid in Korean cabbage 14 days before harvest (0.80 mg/kg) was lower than that specified by the MFDS-MRL (Ministry of Food and Drug Safety-Maximum Residue Limit, 2.0 mg/kg) and should be recommended as the safe preharvest-interval application limit. The hazard quotient showed low toxicity (70.58%) during the risk assessment study of cyazofamid.

Complementary approach for accurate determination of carbon isotopic compositions in γ-hydroxybutyric acid using gas chromatography/combustion-isotope ratio mass spectrometry.

RATIONALE: γ-Hydroxybutyric acid (GHB) is a naturally endogenous neurotransmitter that is popular as a recreational drug due to its sedative, hypnotic, and euphoric effects. GHB derived from endogenous production or exogenous ingestion has been effectively discriminated by carbon isotopic compositions (δ13 C values) through gas chromatography/combustion-isotope ratio mass spectrometry (GC/C-IRMS). However, an unintended uncertainty of isotopic signatures caused by a wide range of GHB quantities remains unsolved when using only single-isotope corrections of the di-TMS derivative. METHODS: The δ13 C values of the original GHB standard were first determined by elemental analyzer/isotope ratio mass spectrometry (EA/IRMS). The δ13 C values of silylated GHB in concentrations from 10 to 500 ppm were determined by GC/C-IRMS. With respect to the silylated reaction products, the correction of δ13 C values for the introduced carbons was calculated from a stoichiometric mass balance equation. RESULTS: The results showed a significant quantity-dependent trend in δ13 C values of introduced carbon (δ13 Cdi-TMS values) with increased GHB standard concentrations (r2 = 0.70, p <0.05). We applied a logarithmic equation to determine isotopic data in low-GHB urine specimens from five healthy female volunteers. The δ13 CGHB values in urine samples corrected with quantity-dependent δ13 Cdi-TMS values were different by an average of 2.7‰ from those corrected with single δ13 Cdi-TMS values (p <0.05). CONCLUSIONS: Our results suggest that the overall residual amount-dependent isotope fractionation should be mathematically corrected by the logarithmic function and this may improve the reliability of isotopic analysis to evaluate the origin of GHB before applying the approach to routine toxicological and forensic studies.

Correction to: Differentiation of endogenous and exogenous γ-Hydroxybutyrate in rat and human urine by GC/C/IRMS.

The above article was published online with incorrect author names. The right spelling should be Dong-Hun Lee instead of Donghun Lee, Sanggil Choe instead of Sanggil Choi. The correct names are presented here. The original article has been corrected.

Differentiation of endogenous and exogenous γ-Hydroxybutyrate in rat and human urine by GC/C/IRMS.

Gamma (γ)-hydroxybutyric acid (GHB) has been reported to be an endogenous compound in the mammalian brain. It used to treat symptoms of alcohol, opioid, and drug withdrawal and cataplexy of narcolepsy. However, it is often used for criminal purposes because it is colorless, tasteless, and has short half-life. For this reason, there is a need for a method of distinguishing between endogenous and exogenous GHB administration. Therefore, urine from rat before administration of GHB and GHB urine after the single intraperitoneal injection of GHB as 30 mg/100 g were collected from Sprague-Dawley rats (7 weeks old, 10 males and females). Negative control urine, urine from individuals suspected of taking GHB, and urine from victims who were GHB-involved crime were collected. In urine samples, GHB was extracted with two-step SPE and collected fraction was derivatized and analyzed by GC/MS and GC/C/IRMS. In GC/MS and GC/C/IRMS analysis of rat urine, there was a statistically significant difference between urine from rat before administration of GHB and GHB rat urine (p < 0.05). In GC/MS analysis of human urine samples, there was no significant difference among human urine groups (negative control, suspects' urine, and victims' urine), but in GC/C/IRMS analysis of human urine samples, there was a statistically significant difference among human urine groups (p = 0.0001). Through these results, GC/C/IRMS can be more effective tool to identify endogenous and exogenous GHB in urine than GC/MS. This study can build a drug management system in forensic investigation agency and offer interpretation method to forensic science and court.

Exposure to 835 MHz radiofrequency electromagnetic field induces autophagy in hippocampus but not in brain stem of mice.

The exploding popularity of mobile phones and their close proximity to the brain when in use has raised public concern regarding possible adverse effects from exposure to radiofrequency electromagnetic fields (RF-EMF) on the central nervous system. Numerous studies have suggested that RF-EMF emitted by mobile phones can influence neuronal functions in the brain. Currently, there is still very limited information on what biological mechanisms influence neuronal cells of the brain. In the present study, we explored whether autophagy is triggered in the hippocampus or brain stem after RF-EMF exposure. C57BL/6 mice were exposed to 835 MHz RF-EMF with specific absorption rates (SAR) of 4.0 W/kg for 12 weeks; afterward, the hippocampus and brain stem of mice were dissected and analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated that several autophagic genes, which play key roles in autophagy regulation, were significantly upregulated only in the hippocampus and not in the brain stem. Expression levels of LC3B-II protein and p62, crucial autophagic regulatory proteins, were significantly changed only in the hippocampus. In parallel, transmission electron microscopy (TEM) revealed an increase in the number of autophagosomes and autolysosomes in the hippocampal neurons of RF-EMF-exposed mice. The present study revealed that autophagy was induced in the hippocampus, not in the brain stem, in 835 MHz RF-EMF with an SAR of 4.0 W/kg for 12 weeks. These results could suggest that among the various adaptation processes to the RF-EMF exposure environment, autophagic degradation is one possible mechanism in specific brain regions.

Pyruvate dehydrogenase kinase 4 deficiency attenuates cisplatin-induced acute kidney injury.

Clinical prescription of cisplatin, one of the most widely used chemotherapeutic agents, is limited by its side effects, particularly tubular injury-associated nephrotoxicity. Since details of the underlying mechanisms are not fully understood, we investigated the role of pyruvate dehydrogenase kinase (PDK) in cisplatin-induced acute kidney injury. Among the PDK isoforms, PDK4 mRNA and protein levels were markedly increased in the kidneys of mice treated with cisplatin, and c-Jun N-terminal kinase activation was involved in cisplatin-induced renal PDK4 expression. Treatment with the PDK inhibitor sodium dichloroacetate (DCA) or genetic knockout of PDK4 attenuated the signs of cisplatin-induced acute kidney injury, including apoptotic morphology of the kidney tubules along with numbers of TUNEL-positive cells, cleaved caspase-3, and renal tubular injury markers. Cisplatin-induced suppression of the mitochondrial membrane potential, oxygen consumption rate, expression of electron transport chain components, cytochrome c oxidase activity, and disruption of mitochondrial morphology were noticeably improved in the kidneys of DCA-treated or PDK4 knockout mice. Additionally, levels of the oxidative stress marker 4-hydroxynonenal and mitochondrial reactive oxygen species were attenuated, whereas superoxide dismutase 2 and catalase expression and glutathione synthetase and glutathione levels were recovered in DCA-treated or PDK4 knockout mice. Interestingly, lipid accumulation was considerably attenuated in DCA-treated or PDK4 knockout mice via recovered expression of peroxisome proliferator-activated receptor-α and coactivator PGC-1α, which was accompanied by recovery of mitochondrial biogenesis. Thus, PDK4 mediates cisplatin-induced acute kidney injury, suggesting that PDK4 might be a therapeutic target for attenuating cisplatin-induced acute kidney injury.