ESSAYS ON LINKAGES BETWEEN CAPITAL FLOWS, LEVERAGE, AND THE REAL ECONOMY

Europe experienced a sovereign debt crisis starting in 2010, in which perceived default risk and interest rates on government bonds soared in many countries, leading to recessions. This episode was preceded by a steady rise in the ratio of corporate debt to GDP, suggesting that private sector leverage may be a contributing factor to rising sovereign risk. In the main essay, I find that corporate debt causally affects sovereign default risk and show that this corporate-sovereign debt nexus is an important amplification mechanism driven by externalities that call for macroprudential policies. I run instrumental variable regressions to estimate a causal relationship running from aggregate corporate leverage to sovereign spreads. I use the weighted sum of idiosyncratic shocks to top 50 large firms in each Eurozone country as an instrument for aggregate corporate leverage to rule out potential reverse causality and omitted variable bias. The regressions suggest that rising corporate leverage causes sovereign spreads to rise, which confirms the existence of the corporate-sovereign nexus. To understand the mechanism, I build a model in which both firms and the government can default. When corporate debt increases, tax revenues are expected to be lower, as firms stop paying taxes and dividends when they default, which raises sovereign default risk. This tax revenue channel is supported by empirical evidence. Country-level tax revenue regressions show that increases in corporate debt-to-GDP ratios reduce future tax revenue growth. Difference-in-difference regressions using firm-level data suggest that highly-leveraged firms reduce tax payments more compared to less-leveraged firms in response to the 2008 global financial crisis. Moreover, I analyze an externality that arises from firms' limited liability, which is distinct from the pecuniary and aggregate demand externalities. I find that there exist time-consistent optimal policies that correct the limited liability externality. A quantitative model calibrated to six Eurozone countries shows that such policies consists of a low constant debt tax rate together with transfers and investment credits to firms during the crisis. Implementing these policies alleviates the corporate-sovereign linkage, so that the number of defaulting firms decreases, and the government has enough fiscal space to provide transfers to households suffering from low consumption. Furthermore, practical policies such as either constant or cyclical debt tax schedules can correct overborrowing externalities. However, a countercyclical debt policy (which raises the debt tax rate during corporate credit booms) induces more firm defaults during crises, and thus it is less effective than constant and procyclical debt tax policies. This suggests that policymakers should be cautious about implementing countercyclical debt tax policies such as countercyclical capital buffers, and should even consider relaxing regulations when corporate default risk is high. The second essay (co-authored) documents new facts on the relationship between sector-level capital flows and sectoral leverage. We highlight the interconnections between different approaches and argue that harmonization of the macro and micro approaches can yield a more complete understanding of these effects of capital flows on country-, sector- and firm/bank-level leverage associated with credit booms and busts. The third essay (co-authored) uses a historical quasi-experiment in the Ottoman Empire to estimate the causal effect of trade shocks on capital flows. We argue that fluctuations in regional rainfall within the Ottoman Empire capture the exogenous variation in exports from the Empire to Germany, France, and the U.K., during 1859-1913. Our identification is based on the following historical facts: First, only surplus production was allowed to be exported in the Ottoman Empire (provisionistic policy). Second, different products grew in different regions that were subject to variation in rainfall. Third, Germany, France, and the U.K. imported these different products. When a given region of the Empire gets more rainfall than others, the resulting surplus production is exported to countries with higher ex-ante export shares for those products, and this leads to higher foreign investment by those countries in the Ottoman Empire. Our findings support theories predicting complementarity between trade and finance, where causality runs from trade to capital flows

The Effect of Milrinone on the Right Ventriclular Function in Patients with Reduced Right Ventricular Function Undergoing Off-pump Coronary Artery Bypass Graft Surgery

This investigation evaluated the effect of continuous milrinone infusion on right ventriclular (RV) function during off-pump coronary artery bypass graft (OPCAB) surgery in patients with reduced RV function. Fifty patients scheduled for OPCAB, with thermodilution RV ejection fraction (RVEF) <35% after anesthesia induction, were randomly allocated to either milrinone (0.5 µg/kg/min) or control (saline) group. Hemodynamic variables and RV volumetric data measured by thermodilution method were collected as follows: after anesthesia induction (T1); 10 min after heart displacement for obtuse marginal artery anastomosis (T2); after pericardial closure (T3). Cardiac index and heart rate increased and systemic vascular resistance significantly decreased in milrinone group at T2. Initially lower RVEF of milrinone group was eventually comparable to control group after milrinone infusion. RVEF did not significantly change at T2 and T3 in both groups. RV end-diastolic volume in milrinone group consistently decreased from the baseline at T2 and T3. Continuous infusion of milrinone without a bolus demonstrated potentially beneficial effect on cardiac output and RV afterload in patients with reduced RV function during OPCAB. However, aggressive augmentation of intravascular volume seems to be necessary to maximize the effect of the milrinone in these patients

Effects of exercise on obesity-induced mitochondrial dysfunction in skeletal muscle

Obesity is known to induce inhibition of glucose uptake, reduction of lipid metabolism, and progressive loss of skeletal muscle function, which are all as- sociated with mitochondrial dysfunction in skeletal muscle. Mitochondria are dy- namic organelles that regulate cellular metabolism and bioenergetics, including ATP production via oxidative phosphorylation. Due to these critical roles of mitochon- dria, mitochondrial dysfunction results in various diseases such as obesity and type 2 diabetes. Obesity is associated with impairment of mitochondrial function (e.g., decrease in O2 respiration and increase in oxidative stress) in skeletal muscle. The bal- ance between mitochondrial fusion and fission is critical to maintain mitochondrial homeostasis in skeletal muscle. Obesity impairs mitochondrial dynamics, leading to an unbalance between fusion and fission by favorably shifting fission or reducing fusion proteins. Mitophagy is the catabolic process of damaged or unnecessary mito- chondria. Obesity reduces mitochondrial biogenesis in skeletal muscle and increases accumulation of dysfunctional cellular organelles, suggesting that mitophagy does not work properly in obesity. Mitochondrial dysfunction and oxidative stress are reported to trigger apoptosis, and mitochondrial apoptosis is induced by obesity in skeletal muscle. It is well known that exercise is the most effective intervention to protect against obesity. Although the cellular and molecular mechanisms by which exercise protects against obesity-induced mitochondrial dysfunction in skeletal mus- cle are not clearly elucidated, exercise training attenuates mitochondrial dysfunction, allows mitochondria to maintain the balance between mitochondrial dynamics and mitophagy, and reduces apoptotic signaling in obese skeletal muscle

High frequencies of Y-chromosome haplogroup O2b-SRY465 lineages in Korea: a genetic perspective on the peopling of Korea

<p>Abstract</p> <p>Background</p> <p>Koreans are generally considered a Northeast Asian group, thought to be related to Altaic-language-speaking populations. However, recent findings have indicated that the peopling of Korea might have been more complex, involving dual origins from both southern and northern parts of East Asia. To understand the male lineage history of Korea, more data from informative genetic markers from Korea and its surrounding regions are necessary. In this study, 25 Y-chromosome single nucleotide polymorphism markers and 17 Y-chromosome short tandem repeat (Y-STR) loci were genotyped in 1,108 males from several populations in East Asia.</p> <p>Results</p> <p>In general, we found East Asian populations to be characterized by male haplogroup homogeneity, showing major Y-chromosomal expansions of haplogroup O-M175 lineages. Interestingly, a high frequency (31.4%) of haplogroup O2b-SRY465 (and its sublineage) is characteristic of male Koreans, whereas the haplogroup distribution elsewhere in East Asian populations is patchy. The ages of the haplogroup O2b-SRY465 lineages (~9,900 years) and the pattern of variation within the lineages suggested an ancient origin in a nearby part of northeastern Asia, followed by an expansion in the vicinity of the Korean Peninsula. In addition, the coalescence time (~4,400 years) for the age of haplogroup O2b1-47z, and its Y-STR diversity, suggest that this lineage probably originated in Korea. Further studies with sufficiently large sample sizes to cover the vast East Asian region and using genomewide genotyping should provide further insights.</p> <p>Conclusions</p> <p>These findings are consistent with linguistic, archaeological and historical evidence, which suggest that the direct ancestors of Koreans were proto-Koreans who inhabited the northeastern region of China and the Korean Peninsula during the Neolithic (8,000-1,000 BC) and Bronze (1,500-400 BC) Ages.</p

Mechanism and treatment for learning and memory deficits in mouse models of Noonan syndrome.

In Noonan syndrome (NS) 30-50% of subjects show cognitive deficits of unknown etiology and with no known treatment. Here, we report that knock-in mice expressing either of two NS-associated mutations in Ptpn11, which encodes the nonreceptor protein tyrosine phosphatase Shp2, show hippocampal-dependent impairments in spatial learning and deficits in hippocampal long-term potentiation (LTP). In addition, viral overexpression of an NS-associated allele PTPN11(D61G) in adult mouse hippocampus results in increased baseline excitatory synaptic function and deficits in LTP and spatial learning, which can be reversed by a mitogen-activated protein kinase kinase (MEK) inhibitor. Furthermore, brief treatment with lovastatin reduces activation of the GTPase Ras-extracellular signal-related kinase (Erk) pathway in the brain and normalizes deficits in LTP and learning in adult Ptpn11(D61G/+) mice. Our results demonstrate that increased basal Erk activity and corresponding baseline increases in excitatory synaptic function are responsible for the LTP impairments and, consequently, the learning deficits in mouse models of NS. These data also suggest that lovastatin or MEK inhibitors may be useful for treating the cognitive deficits in NS

A Case of Pituitary Metastasis from Breast Cancer That Presented as Left Visual Disturbance

Tumors that metastasize to the pituitary gland are unusual, and are typically seen in elderly patients with diffuse malignant disease. The most common metastases to the pituitary are from primary breast and lung cancers. We report a 65-year-old woman with pituitary metastasis from breast cancer who presented with recent-onset left progressive deterioration of visual acuity and visual field. The clinical diagnosis was made after brain and sellar magnetic resonance imaging showed a large sellar mass compressing the optic chiasm and invading the pituitary stalk. An otorhinolaryngology and neurosurgery team removed the tumor via a transsphenoidal approach, and this procedure obtained symptomatic relief. Postoperatively, metastasis from breast invasive ductal adenocarcinoma was confirmed histologically. We report this unusual case with a review of the relevant literature

Therapeutic genome editing for Charcot-marie-tooth disease type 1a

Charcot-Marie-Tooth 1A (CMT1A) is the most common inherited neuropathy without a known therapy, which is caused by a 1.4 Mb duplication on human chromosome 17, which includes the gene encoding the peripheral myelin protein of 22 kDa (PMP22). Overexpressed PMP22 protein from its gene duplication is thought to cause demyelination and subsequently axonal degeneration in the peripheral nervous system (PNS). Here, we targeted regulatory region of human PMP22 to normalize overexpressed PMP22 level in C22 mice, a mouse model of CMT1A harboring multi copies of human PMP22. Direct local intraneural delivery of CRISPR/Cas9 designed to target TATA-box of PMP22 before the onset of disease, downregulates gene expression of PMP22 and preserves both myelin and axons. Notably, the same approach was effective in partial rescue of demyelination even after the onset of disease. Collectively, our data present a potential therapeutic efficacy of CRISPR/Cas9-mediated targeting of regulatory region of PMP22 to treat CMT1A. Please click Additional Files below to see the full abstract

Exercise Training Attenuates Ovariectomy-Induced Alterations in Skeletal Muscle Remodeling, Apoptotic Signaling, and Atrophy Signaling in Rat Skeletal Muscle

Purpose The effects of aerobic exercise training on soleus muscle morphology, mitochondria-mediated apoptotic signaling, and atrophy/hypertrophy signaling in ovariectomized rat skeletal muscle were investigated. Methods Female Sprague-Dawley rats were divided into control (CON), ovariectomy (OVX), and ovariectomy plus exercise (OVX+EX) groups. After ovarian excision, exercise training was performed using a rat treadmill at 20 m/min, 50 min/day, 5 days/week for 12 weeks. Protein levels of mitochondria-mediated apoptotic signaling and atrophy/hypertrophy signaling in the skeletal muscle (soleus) were examined through western immunoblot analysis. Results The number of myocytes and myocyte cross-sectional area (CSA) were increased and the extramyocyte space was decreased in the OVX group compared to those in the CON group. However, aerobic exercise training significantly increased myocyte CSA and decreased extramyocyte space in the OVX+EX group compared to those in the OVX group. The protein levels of proapoptotic signaling and muscle atrophy signaling were significantly increased, whereas the protein levels of muscle hypertrophy signaling were significantly decreased in the OVX group compared to that in the CON group. Aerobic exercise training significantly decreased the protein levels of proapoptotic signaling and increased the protein level of antiapoptotic protein in the OVX+EX group compared to that in the OVX group. Aerobic exercise training significantly increased the protein levels of hypertrophy signaling and decreased protein levels of atrophy signaling in the OVX+EX group compared to those in the OVX group. Conclusions Treadmill exercise improved estrogen deficiency-induced impairment in skeletal muscle remodeling, mitochondria-mediated apoptotic signaling, and atrophy/hypertrophy signaling in skeletal muscle