Adolescent Parvalbumin Expression in the Left Orbitofrontal Cortex Shapes Sociability in Female Mice.

The adolescent social experience is essential for the maturation of the prefrontal cortex in mammalian species. However, it still needs to be determined which cortical circuits mature with such experience and how it shapes adult social behaviors in a sex-specific manner. Here, we examined social-approaching behaviors in male and female mice after postweaning social isolation (PWSI), which deprives social experience during adolescence. We found that the PWSI, particularly isolation during late adolescence, caused an abnormal increase in social approaches (hypersociability) only in female mice. We further found that the PWSI female mice showed reduced parvalbumin (PV) expression in the left orbitofrontal cortex (OFCL). When we measured neural activity in the female OFCL, a substantial number of neurons showed higher activity when mice sniffed other mice (social sniffing) than when they sniffed an object (object sniffing). Interestingly, the PWSI significantly reduced both the number of activated neurons and the activity level during social sniffing in female mice. Similarly, the CRISPR/Cas9-mediated knockdown of PV in the OFCL during late adolescence enhanced sociability and reduced the social sniffing-induced activity in adult female mice via decreased excitability of PV+ neurons and reduced synaptic inhibition in the OFCL Moreover, optogenetic activation of excitatory neurons or optogenetic inhibition of PV+ neurons in the OFCL enhanced sociability in female mice. Our data demonstrate that the adolescent social experience is critical for the maturation of PV+ inhibitory circuits in the OFCL; this maturation shapes female social behavior via enhancing social representation in the OFCL SIGNIFICANCE STATEMENT Adolescent social isolation often changes adult social behaviors in mammals. Yet, we do not fully understand the sex-specific effects of social isolation and the brain areas and circuits that mediate such changes. Here, we found that adolescent social isolation causes three abnormal phenotypes in female but not male mice: hypersociability, decreased PV+ neurons in the left orbitofrontal cortex (OFCL), and decreased socially evoked activity in the OFCL Moreover, parvalbumin (PV) deletion in the OFCL in vivo caused the same phenotypes in female mice by increasing excitation compared with inhibition within the OFCL Our data suggest that adolescent social experience is required for PV maturation in the OFCL, which is critical for evoking OFCL activity that shapes social behaviors in female mice.

Preoperative low muscle mass and early postoperative outcomes in children undergoing living donor liver transplantation: A retrospective study.

Low skeletal muscle mass may develop in children with end-stage liver disease, affecting postoperative outcomes. We retrospectively investigated whether preoperative low muscle mass was associated with early postoperative outcomes in pediatric patients undergoing living donor liver transplantation (LDLT). Electronic medical records of children (age below 12 y) who underwent LDLT between February 1, 2007, and January 31, 2018, were reviewed. The cross-sectional areas of psoas, quadratus lumborum, and erector spinae muscles at the level of fourth-fifth lumbar intervertebral disks were measured using abdominal CT images, divided by the square of the height and were added to obtain the total skeletal muscle index (TSMI). The patients were divided into two groups according to the median TSMI in the second quintile (1859.1 mm 2 /m 2 ). Complications in the early postoperative period (within 30 d after surgery) classified as Clavien-Dindo grade 3 or higher were considered major complications. Logistic regression analyses were performed to determine the association between preoperative low muscle mass and early postoperative outcomes. In the study population of 123 patients (median age, 14 mo; range, 8-38 mo) who underwent LDLT, 29% and 71% were classified in the low (mean TSMI, 1642.5 ± 187.0 mm 2 /m 2 ) and high (mean TSMI 2188.1 ± 273.5 mm 2 /m 2 ) muscle mass groups, respectively. The rates of major complications, mechanical ventilation >96 hours, intensive care unit stay >14 days, hospital stay >30 days, and in-hospital mortality were not significantly different between the 2 groups. Additionally, adverse outcomes according to pediatric end-stage liver disease scores and sex were not significantly different between the 2 groups. In conclusion, preoperative low muscle mass defined by TSMI was not associated with early postoperative outcomes in pediatric patients undergoing LDLT.

Inhibition of late sodium current via PI3K/Akt signaling prevents cellular remodeling in tachypacing-induced HL-1 atrial myocytes.

An aberrant late sodium current (INa,Late) caused by a mutation in the cardiac sodium channel (Nav1.5) has emerged as a contributor to electrical remodeling that causes susceptibility to atrial fibrillation (AF). Although downregulation of phosphoinositide 3-kinase (PI3K)/Akt signaling is associated with AF, the molecular mechanisms underlying the negative regulation of INa,Late in AF remain unclear, and potential therapeutic approaches are needed. In this work, we constructed a tachypacing-induced cellular model of AF by exposing HL-1 myocytes to rapid electrical stimulation (1.5 V/cm, 4 ms, 10 Hz) for 6 h. Then, we gathered data using confocal Ca2+ imaging, immunofluorescence, patch-clamp recordings, and immunoblots. The tachypacing cells displayed irregular Ca2+ release, delayed afterdepolarization, prolonged action potential duration, and reduced PI3K/Akt signaling compared with controls. Those detrimental effects were related to increased INa,Late and were significantly mediated by treatment with the INa,Late blocker ranolazine. Furthermore, decreased PI3K/Akt signaling via PI3K inhibition increased INa,Late and subsequent aberrant myocyte excitability, which were abolished by INa,Late inhibition, suggesting that PI3K/Akt signaling is responsible for regulating pathogenic INa,Late. These results indicate that PI3K/Akt signaling is critical for regulating INa,Late and electrical remodeling, supporting the use of PI3K/Akt-mediated INa,Late as a therapeutic target for AF.

Association Between Preoperative Sarcopenia and Early Postoperative Outcomes in Pediatric Patients Undergoing Total Correction of Tetralogy of Fallot: A Retrospective Cohort Study.

OBJECTIVES: To identify the association between preoperative low muscle mass and early postoperative outcomes in pediatric patients undergoing total correction of tetralogy of Fallot (TOF). DESIGN: A retrospective cohort study. SETTING: A single university hospital in Seoul, South Korea. PARTICIPANTS: Pediatric patients (≤3 years) who underwent total correction of TOF between May 2008 and February 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cross-sectional areas of the pectoralis and erector spinae muscles were measured using preoperative chest computed tomography (CT) scans, and adjusted to body surface area to define muscle mass index. The patients were divided into sarcopenia, presarcopenia, and no sarcopenia groups based on cutoff values determined using the mean and SD of the muscle mass index in the third z-weight quintile. Of a total of 330 patients included in the final analysis, 13 were associated with the sarcopenia group, 57 in the presarcopenia group, and 260 in the no sarcopenia group. The sarcopenia group exhibited a higher incidence of major adverse events than the presarcopenia and no sarcopenia groups, respectively (38% v 25% v 18%; p = 0.033). Logistic regression analyses revealed that only younger age at the time of surgery was significantly associated with major adverse events (odds ratio 0.82; 95% CI 0.72-0.94, p = 0.003). CONCLUSIONS: The incidence of sarcopenia, as assessed by preoperative chest CT, was low in pediatric patients undergoing total correction of TOF, and preoperative sarcopenia did not predict early postoperative major adverse events.

Exosomal miR-205-5p Improves Endometrial Receptivity by Upregulating E-Cadherin Expression through ZEB1 Inhibition.

Endometrial receptivity is a complex process that prepares the uterine endometrium for embryo implantation; insufficient endometrial receptivity is one of the causes of implantation failure. Here, we analyzed the microRNA expression profiles of exosomes derived from both receptive (RL95-2) and non-receptive (AN3-CA) endometrial epithelial cell (EEC) lines to identify exosomal miRNAs closely linked to endometrial receptivity. Among the 466 differentially expressed miRNAs, miR-205-5p was the most highly expressed in exosomes secreted from receptive RL95-2 cells. miR-205-5p, enriched at the adhesive junction, was closely related to endometrial receptivity. ZEB1, a transcriptional repressor of E-cadherin associated with endometrial receptivity, was identified as a direct target of miR-205-5p. miR-205-5p expression was significantly lower in the endometrial tissues of infertile women than in that of non-infertile women. In vivo, miR-205-5p expression was upregulated in the post-ovulatory phase, and its inhibitor reduced embryo implantation. Furthermore, administration of genetically modified exosomes overexpressing miR-205-5p mimics upregulated E-cadherin expression by targeting ZEB1 and improved spheroid attachment of non-receptive AN3-CA cells. These results suggest that the miR-205-5p/ZEB1/E-cadherin axis plays an important role in regulating endometrial receptivity. Thus, the use of exosomes harboring miR-205-5p mimics can be considered a potential therapeutic approach for improving embryo implantation.

MicroRNA-323-5p Involved in Dexmedetomidine Preconditioning Impart Neuroprotection.

Background and Objectives: Cerebral ischemia is one of the major preoperative complications. Dexmedetomidine is a well-known sedative-hypnotic agent that has potential organ-protective effects. We examine the miRNAs associated with preconditioning effects of dexmedetomidine in cerebral ischemia. Materials and Methods: Transient infarcts were induced in mice via reperfusion after temporary occlusion of one side of the middle cerebral artery. A subset of these mice was exposed to dexmedetomidine prior to cerebral infarction and miRNA profiling of the whole brain was performed. We administered dexmedetomidine and miRNA-323-5p mimic/inhibitor to oxygen-glucose deprivation/reoxygenation astrocytes. Additionally, we administered miR-323-5p mimic and inhibitor to mice via intracerebroventricular injection 2 h prior to induction of middle cerebral artery occlusion. Results: The infarct volume was significantly lower in the dexmedetomidine-preconditioned mice. Analysis of brain samples revealed an increased expression of five miRNAs and decreased expression of three miRNAs in the dexmedetomidine-pretreated group. The viability of cells significantly increased and expression of miR-323-5p was attenuated in the dexmedetomidine-treated oxygen-glucose deprivation/reoxygenation groups. Transfection with anti-miR-323-5p contributed to increased astrocyte viability. When miRNA-323-5p was injected intraventricularly, infarct volume was significantly reduced when preconditioned with the miR-323-5p inhibitor compared with mimic and negative control. Conclusions: Dexmedetomidine has a protective effect against transient neuronal ischemia-reperfusion injury and eight specific miRNAs were profiled. Also, miRNA-323-5p downregulation has a cell protective effect under ischemic conditions both in vivo and in vitro. Our findings suggest the potential of the miR-323-5p inhibitor as a therapeutic agent against cerebral infarction.

Dexamethasone-Loaded Hydrogels Improve Motor and Cognitive Functions in a Rat Mild Traumatic Brain Injury Model.

Functional recovery following traumatic brain injury (TBI) is limited due to progressive neuronal damage resulting from secondary injury-associated neuroinflammation. Steroidal anti-inflammatory drugs, such as dexamethasone (DX), can reduce neuroinflammation by activated microglia and infiltrated macrophages. In our previous work, we developed hydrolytically degradable poly(ethylene) glycol-bis-(acryloyloxy acetate) (PEG-bis-AA) hydrogels with dexamethasone (DX)-conjugated hyaluronic acid (HA-DXM) and demonstrated that dexamethasone-loaded hydrogels (PEG-bis-AA/HA-DXM) can reduce neuroinflammation, apoptosis, and lesion volume and improve neuronal cell survival and motor function recovery at seven days post-injury (DPI) in a rat mild-TBI model. In this study, we investigate the effects of the local application of PEG-bis-AA/HA-DXM hydrogels on motor function recovery at 7 DPI and cognitive functional recovery as well as secondary injury at 14 DPI in a rat mild-CCI TBI model. We observed that PEG-bis-AA/HA-DXM-treated animals exhibit significantly improved motor functions by the rotarod test and cognitive functions by the Morris water maze test compared to untreated TBI animals. We also observed that PEG-bis-AA/HA-DXM hydrogels reduce the inflammatory response, apoptosis, and lesion volume compared to untreated animals at 14 DPI. Therefore, PEG-bis-AA/HA-DXM hydrogels can be promising a therapeutic intervention for TBI treatment.

The miR-182-5p/NDRG1 Axis Controls Endometrial Receptivity through the NF-κB/ZEB1/E-Cadherin Pathway.

Endometrial receptivity is essential for successful pregnancy, and its impairment is a major cause of embryo-implantation failure. MicroRNAs (miRNAs) that regulate epigenetic modifications have been associated with endometrial receptivity. However, the molecular mechanisms whereby miRNAs regulate endometrial receptivity remain unclear. Therefore, we investigated whether miR-182 and its potential targets influence trophoblast cell attachment. miR-182 was expressed at lower levels in the secretory phase than in the proliferative phase of endometrium tissues from fertile donors. However, miR-182 expression was upregulated during the secretory phase in infertile women. Transfecting a synthetic miR-182-5p mimic decreased spheroid attachment of human JAr choriocarcinoma cells and E-cadherin expression (which is important for endometrial receptivity). miR-182-5p also downregulated N-Myc downstream regulated 1 (NDRG1), which was studied further. NDRG1 was upregulated in the secretory phase of the endometrium tissues and induced E-cadherin expression through the nuclear factor-κΒ (NF-κΒ)/zinc finger E-box binding homeobox 1 (ZEB1) signaling pathway. NDRG1-overexpressing or -depleted cells showed altered attachment rates of JAr spheroids. Collectively, our findings indicate that miR-182-5p-mediated NDRG1 downregulation impaired embryo implantation by upregulating the NF-κΒ/ZEB1/E-cadherin pathway. Hence, miR-182-5p is a potential biomarker for negative selection in endometrial receptivity and a therapeutic target for successful embryo implantation.

Suppression of Osteoarthritis progression by post-natal Induction of Nkx3.2.

Osteoarthritis (OA) is an incurable joint disease affecting 240 million elderly population, and major unmet medical needs exist for better therapeutic options for OA. During skeletal development, Nkx3.2 has been shown to promote chondrocyte differentiation and survival, but to suppress cartilage hypertrophy and blood vessel invasion. Here we show that Nkx3.2 plays a key role in osteoarthritis (OA) pathogenesis. Marked reduction of Nkx3.2 expression was observed in three different murine OA models. Consistent with these findings, analyses of surgery-induced and age-driven OA models revealed that cartilage-specific post-natal induction of Nkx3.2 can suppress OA progression in mice. These results suggest that Nkx3.2 may serve as a promising target for OA drug development.

The role of a suburban forest in controlling vertical trace gas and OH reactivity distributions - a case study for the Seoul metropolitan area.

We present trace gas vertical profiles observed by instruments on the NASA DC-8 and at a ground site during the Korea-US air quality study (KORUS) field campaign in May to June 2016. We focus on the region near the Seoul metropolitan area and its surroundings where both anthropogenic and natural emission sources play an important role in local photochemistry. Integrating ground and airborne observations is the major research goal of many atmospheric chemistry field campaigns. Although airborne platforms typically aim to sample from near surface to the free troposphere, it is difficult to fly very close to the surface especially in environments with complex terrain or a populated area. A detailed analysis integrating ground and airborne observations associated with specific concentration footprints indicates that reactive trace gases are quickly oxidized below an altitude of 700 m. The total OH reactivity profile has a rapid decay in the lower part of troposphere from surface to the lowest altitude (700 m) sampled by the NASA DC-8. The decay rate is close to that of very reactive biogenic volatile organic compounds such as monoterpenes. Therefore, we argue that photochemical processes in the bottom of the boundary layer, below the typical altitude of aircraft sampling, should be thoroughly investigated to properly assess ozone and secondary aerosol formation.

Use of a High-Flow Nasal Cannula in a Child With a Functional Single Ventricle and Difficult Airway.

Inducing anesthesia and securing the airway without disrupting the patient's hemodynamic state are challenging in pediatric patients with a functional single ventricle (FSV). Here, the authors report effective use of a high-flow nasal cannula (HFNC) as a tool in providing oxygen supplementation for airway management in pediatric FSV patients with a history of a difficult airway. A female patient, aged 5 years 7 months, was admitted for extracardiac conduit Fontan procedure. The patient had a history of multiple failed attempts at endotracheal intubation and was diagnosed with retrognathia and severe oral trismus of less than 1 finger width. The patient had another event of mask ventilation failure after propofol sedation during the preoperative computed tomography scan a day before the surgery. The patient's preoperative cardiac catheterization report revealed that the Qp/Qs ratio of 0.82 at room air, and the patient's peripheral oxygen saturation (SpO2) ranged from 70% to 80% at room air. On entering the operating room, the preoxygenation process began with HFNC at an oxygen flow of 16 L/min, with a fraction of inspired oxygen (FIO2) set at 95% after light sedation with an intravenous bolus of midazolam, 0.1 mg/kg. After 4 minutes of applying HFNC, with SpO2 rising from 76% to 98%, anesthetic medications were administered intravenously without a neuromuscular blocking agent to preserve spontaneous breathing. The patient was not ventilated with a facemask but instead left with HFNC in place for continuous supplemental oxygenation. The patient's airway was secured in a single attempt in 80 seconds. HFNC is an ideal option for oxygen supplementation during airway management of pediatric FSV patients, as their balance of pulmonary and systemic flow is perturbed easily by subtle physiologic alteration and therapeutic maneuvers during the induction of general anesthesia and highly susceptible to rapid desaturation and cardiovascular collapse, and should be considered as having a physiologically difficult airway.

Local delivery of RhoA siRNA by PgP nanocarrier reduces inflammatory response and improves neuronal cell survival in a rat TBI model.

Traumatic brain injury (TBI) is a leading cause of death and disability with complex pathophysiology including prolonged neuroinflammation, apoptosis, and glial scar formation. The upregulation of RhoA is a key factor in the pathological development of secondary injury following TBI. Previously, we developed a novel cationic, amphiphilic copolymer, poly (lactide-co-glycolide)-graft-polyethylenimine (PgP), as a nanocarrier for delivery of therapeutic nucleic acids. In a rat compression spinal cord injury model, delivery of siRNA targeting RhoA (siRhoA) by PgP resulted in RhoA knockdown; reduced astrogliosis and inflammation; and promoted axonal regeneration/sparing. Here, we evaluated the effect of RhoA knockdown by PgP/siRhoA nanoplexes in a rat controlled cortical impact TBI model. A single intraparenchymal injection of PgP/siRhoA nanoplexes significantly reduced RhoA expression, lesion volume, neuroinflammation, and apoptosis, and increased neuronal survival in the ipsilateral cortex. These results suggest that PgP/siRhoA nanoplexes can efficiently knockdown RhoA expression in the injured brain and reduce secondary injury.

Clinical implication of intraoperative ventricular-arterial coupling in pediatric patients undergoing ventricular septal defects repair: A retrospective cohort study.

BACKGROUND: Ventricular-arterial coupling is the ratio of arterial elastance to ventricular end-systolic elastance. AIMS: The objective of this study was to determine the clinical implication of intraoperative ventricular-arterial coupling derived from the pressure-area relationship using transesophageal echocardiography. METHODS: This retrospective study reviewed the medical records of 72 pediatric patients with ventricular septal defects who underwent corrective surgery with cardiopulmonary bypass. The single-beat modified method was used to assess ventricular-arterial coupling. Logistic regression analyses were performed to determine the correlation between ventricular-arterial coupling and early postoperative outcomes, including the maximum vasoactive-inotropic score, length of mechanical ventilation, and length of hospital stay. RESULTS: Ventricular-arterial coupling after cardiopulmonary bypass significantly increased (from 1.0 ± 0.4 to 1.4 ± 0.8, p < .001), indicating a disproportionate increase in the arterial elastance index (from 11.5 ± 5.1 to 19.8 ± 7.5 mmHg/cm2 /m2 , p < .001) compared with the ventricular end-systolic elastance index (from 13.0 ± 6.9 to 16.9 ± 9.0 mmHg/cm2 /m2 , p < .001). Logistic regression analyses revealed that high postoperative ventricular-arterial coupling was independently associated with higher postoperative maximum vasoactive-inotropic score (>10; odds ratio [OR], 8.04; 95% confidence interval [CI], 1.38-46.85, p = .020), longer postoperative mechanical ventilation (>15 h; OR: 11.00; 95% CI: 1.26-96.45, p = .030), and longer postoperative hospital stay (>7 days; OR: 2.98; 95% CI: 1.04-8.58, p = .043). CONCLUSIONS: Ventricular-arterial coupling can be easily obtained from the intraoperative transesophageal echocardiography in pediatric patients undergoing ventricular septal defects repair. High postoperative ventricular-arterial coupling is strongly associated with worse early postoperative outcomes. Ventricular-arterial coupling shows promise as an intraoperative analysis tool that can provide insight into the impact of interventions on cardiovascular performance and identify potential targets for treatment in this population.

Impact of Personal Protective Equipment on Out-of-Hospital Cardiac Arrest Resuscitation in Coronavirus Pandemic.

Background and Objectives: This retrospective study evaluated the clinical impact of enhanced personal protective equipment (PPE) on the clinical outcomes in patients with out-of-hospital cardiac arrest. Moreover, by focusing on the use of a powered air-purifying respirator (PAPR), we investigated the medical personnel's perceptions of wearing PAPR during cardiopulmonary resuscitation. Materials and Methods: According to the arrival time at the emergency department, the patients were categorized into a conventional PPE group (1 August 2019 to 20 January 2020) and an enhanced PPE group (21 January 2020, to 31 August 2020). The primary outcomes of this analysis were the return of spontaneous circulation (ROSC) rate. Additionally, subjective perception of the medical staff regarding the effect of wearing enhanced PPE during cardiopulmonary resuscitation (CPR) was evaluated by conducting a survey. Results: This study included 130 out-of-hospital cardiac arrest (OHCA) patients, with 73 and 57 patients in the conventional and enhanced PPE groups, respectively. The median time intervals to first intubation and to report the first arterial blood gas analysis results were longer in the enhanced PPE group than in the conventional PPE group (3 min vs. 2 min; p = 0.020 and 8 min vs. 3 min; p < 0.001, respectively). However, there were no significant differences in the ROSC rate (odds ratio (OR) = 0.79, 95% confidence interval (CI): 0.38-1.67; p = 0.542) and 1 month survival (OR 0.38, 95% CI: 0.07-2.10; p = 0.266) between the two groups. In total, 67 emergent department (ED) professionals responded to the questionnaire. Although a significant number of respondents experienced inconveniences with PAPR use, they agreed that PAPR was necessary during the CPR procedure for protection and reduction of infection transmission. Conclusion: The use of enhanced PPE, including PAPR, affected the performance of CPR to some extent but did not alter patient outcomes. PAPR use during the resuscitation of OHCA patients might positively impact the psychological stability of the medical staff.

Baseline Systolic versus Diastolic Blood Pressure Dip and Subsequent Visual Field Progression in Normal-Tension Glaucoma.

PURPOSE: To investigate the impact of systolic and diastolic blood pressure (DBP) dip at baseline on subsequent visual field (VF) progression in eyes with normal-tension glaucoma (NTG). DESIGN: Prospective cohort study. PARTICIPANTS: This study included 119 eyes of 119 newly diagnosed NTG patients followed up for at least 2 years (average, 40.4±16.9 months). METHODS: All participants underwent baseline 24-hour ambulatory blood pressure (BP) monitoring and measurements of intraocular pressure (IOP) and at least 5 serial VF examinations. Participants were followed up as outpatients at 4- to 6-month intervals. Visual field progression was defined according to Early Manifest Glaucoma Trial criteria. The associations of VF progression with systolic BP (SBP) and DBP measured during the day and at night and other clinical variables were analyzed. MAIN OUTCOME MEASURES: Factors associated with VF progression over time. RESULTS: During follow-up, 41 eyes (34%) showed VF progression. In the multivariate Cox regression model, lower nighttime trough DBP (hazard ratio, 0.953; P = 0.023) and greater nighttime DBP dip area (time multiplied by nighttime DBP > 10 mmHg less than mean daytime DBP; hazard ratio, 1.017; P = 0.003) at baseline were significant predictors of subsequent VF progression. None of the SBP parameters was associated with VF progression. Nocturnal DBP dip showed a greater association with VF progression than SBP dip. CONCLUSIONS: Nocturnal trough DBP and DBP dip area at baseline are significant predictors of subsequent VF progression in NTG. Nocturnal DBP dip may be more relevant to future VF progression than SBP dip in NTG eyes.

Simultaneous and Synergic Production of Bioavailable Iron and Reactive Iodine Species in Ice.

The bioavailable iron is essential for all living organisms, and the dissolution of iron oxide contained in dust and soil is one of the major sources of bioavailable iron in nature. Iodine in the polar atmosphere is related to ozone depletion, mercury oxidation, and cloud condensation nuclei formation. Here we show that the chemical reaction between iron oxides and iodide (I-) is markedly accelerated to produce bioavailable iron (Fe(II)aq) and tri-iodide (I3-: evaporable in the form of I2) in frozen solution (both with and without light irradiation), while it is negligible in aqueous phase. The freeze-enhanced production of Fe(II)aq and tri-iodide is ascribed to the freeze concentration of iron oxides, iodides, and protons in the ice grain boundaries. The outdoor experiments carried out in midlatitude during a winter day (Pohang, Korea: 36°0' N, 129°19' E) and in an Antarctic environment (King George Island: 62°13' S 58°47' W) also showed the enhanced generation of Fe(II)aq and tri-iodide in ice. This study proposes a previously unknown abiotic mechanism and source of bioavailable iron and active iodine species in the polar environment. The pulse input of bioavailable iron and reactive iodine when ice melts may influence the oceanic primary production and CCN formation.

Electric-Field-Induced Protein Translocation via a Conformational Transition in SecDF: An MD Study.

SecDF is an important component of the Sec protein translocation machinery embedded in the bacterial membrane, which is associated with many functions, such as stabilizing other Sec translocon components within the membrane, maintaining the transmembrane (TM) potential, and facilitating the ATP-independent stage of the translocation mechanism. Related studies suggest that SecDF undergoes functionally important conformational changes that involve mainly its P1-head domain and that these changes are coupled with the proton motive force (Δp). However, there still is not a clear understanding of how SecDF functions, its exact role in the translocation machinery, and how its function is related to Δp. Here, using all-atom molecular dynamics simulations combined with umbrella sampling, we study the P1-head conformational change and how it is coupled to the proton motive force. We report potentials of mean force along a root-mean-square-distance-based reaction coordinate obtained in the presence and absence of the TM electrical potential. Our results show that the interaction of the P1 domain dipole moment with the TM electrical field considerably lowers the free-energy barrier in the direction of F-form to I-form transition.

Selectivity of Neuromodulatory Projections from the Basal Forebrain and Locus Ceruleus to Primary Sensory Cortices.

UNLABELLED: Acetylcholine and noradrenaline are major neuromodulators that affect sensory processing in the cortex. Modality-specific sensory information is processed in defined areas of the cortex, but it is unclear whether cholinergic neurons in the basal forebrain (BF) and noradrenergic neurons in the locus ceruleus (LC) project to and modulate these areas in a sensory modality-selective manner. Here, we mapped BF and LC projections to different sensory cortices of the mouse using dual retrograde tracing. We found that while the innervation of cholinergic neurons into sensory cortices is predominantly modality specific, the projections of noradrenergic neurons diverge onto multiple sensory cortices. Consistent with this anatomy, optogenetic activation of cholinergic neurons in BF subnuclei induces modality-selective desynchronization in specific sensory cortices, whereas activation of noradrenergic LC neurons induces broad desynchronization throughout multiple sensory cortices. Thus, we demonstrate a clear distinction in the organization and function of cholinergic BF and noradrenergic LC projections into primary sensory cortices: cholinergic BF neurons are highly selective in their projections and modulation of specific sensory cortices, whereas noradrenergic LC neurons broadly innervate and modulate multiple sensory cortices. SIGNIFICANCE STATEMENT: Neuromodulatory inputs from the basal forebrain (BF) and locus ceruleus (LC) are widespread in the mammalian cerebral cortex and are known to play important roles in attention and arousal, but little is known about the selectivity of their cortical projections. Using a dual retrobead tracing technique along with optogenetic stimulation, we have identified anatomic and functional differences in the way cholinergic BF neurons and noradrenergic LC neurons project into primary sensory cortices. While BF projections are highly selective to individual sensory cortices, LC projections diverge into multiple sensory cortices. To our knowledge, this is the first definitive proof that BF and LC projections to primary sensory cortices show both anatomic and functional differences in selectivity for modulating cortical activity.

Cartilage-Specific and Cre-Dependent Nkx3.2 Overexpression In Vivo Causes Skeletal Dwarfism by Delaying Cartilage Hypertrophy.

Nkx3.2, the vertebrate homologue of Drosophila bagpipe, has been implicated as playing a role in chondrogenic differentiation. In brief, Nkx3.2 is initially expressed in chondrocyte precursor cells and later during cartilage maturation, its expression is diminished in hypertrophic chondrocytes. In addition to Nkx3.2 expression analyses, previous studies using ex vivo chick embryo cultures and in vitro cell cultures have suggested that Nkx3.2 can suppress chondrocyte hypertrophy. However, it has never been demonstrated that Nkx3.2 functions in regulating chondrocyte hypertrophy during cartilage development in vivo. Here, we show that cartilage-specific and Cre-dependent Nkx3.2 overexpression in mice results in significant postnatal dwarfism in endochondral skeletons, while intramembranous bones remain unaltered. Further, we observed significant delays in cartilage hypertrophy in conditional transgenic ciTg-Nkx3.2 mice. Together, these findings confirm that Nkx3.2 is capable of controlling hypertrophic maturation of cartilage in vivo, and this regulation plays a significant role in endochondral ossification and longitudinal bone growth. J. Cell. Physiol. 232: 78-90, 2017. © 2016 Wiley Periodicals, Inc.

OH reactivity in urban and suburban regions in Seoul, South Korea - an East Asian megacity in a rapid transition.

South Korea has recently achieved developed country status with the second largest megacity in the world, the Seoul Metropolitan Area (SMA). This study provides insights into future changes in air quality for rapidly emerging megacities in the East Asian region. We present total OH reactivity observations in the SMA conducted at an urban Seoul site (May-June, 2015) and a suburban forest site (Sep, 2015). The total OH reactivity in an urban site during the daytime was observed at similar levels (∼15 s(-1)) to those previously reported from other East Asian megacity studies. Trace gas observations indicate that OH reactivity is largely accounted for by NOX (∼50%) followed by volatile organic compounds (VOCs) (∼35%). Isoprene accounts for a substantial fraction of OH reactivity among the comprehensive VOC observational dataset (25-47%). In general, observed total OH reactivity can be accounted for by the observed trace gas dataset. However, observed total OH reactivity in the suburban forest area cannot be largely accounted for (∼70%) by the trace gas measurements. The importance of biogenic VOC (BVOCs) emissions and oxidations used to evaluate the impacts of East Asian megacity outflows for the regional air quality and climate contexts are highlighted in this study.