Mice born to females with oocyte-specific deletion of mitofusin 2 have increased weight gain and impaired glucose homeostasis.

Offspring born to obese and diabetic mothers are prone to metabolic diseases, a phenotype that has been linked to mitochondrial dysfunction and endoplasmic reticulum (ER) stress in oocytes. In addition, metabolic diseases impact the architecture and function of mitochondria-ER contact sites (MERCs), changes which associate with mitofusin 2 (MFN2) repression in muscle, liver and hypothalamic neurons. MFN2 is a potent modulator of mitochondrial metabolism and insulin signaling, with a key role in mitochondrial dynamics and tethering with the ER. Here, we investigated whether offspring born to mice with MFN2-deficient oocytes are prone to obesity and diabetes. Deletion of Mfn2 in oocytes resulted in a profound transcriptomic change, with evidence of impaired mitochondrial and ER function. Moreover, offspring born to females with oocyte-specific deletion of Mfn2 presented increased weight gain and glucose intolerance. This abnormal phenotype was linked to decreased insulinemia and defective insulin signaling, but not mitochondrial and ER defects in offspring liver and skeletal muscle. In conclusion, this study suggests a link between disrupted mitochondrial/ER function in oocytes and increased risk of metabolic diseases in the progeny. Future studies should determine whether MERC architecture and function are altered in oocytes from obese females, which might contribute toward transgenerational transmission of metabolic diseases.

Mitofusin 1 is required for oocyte growth and communication with follicular somatic cells.

Mitochondrial function, largely regulated by the dynamics of this organelle, is inextricably linked to the oocyte health. In comparison with most somatic cells, mitochondria in oocytes are smaller and rounder in appearance, suggesting limited fusion. The functional implications of this distinct morphology, and how changes in the mitochondrial shape translate to mitochondrial function in oogenesis is little understood. We, therefore, asked whether the pro-fusion proteins mitofusins 1 (MFN1) and 2 (MFN2) are required for the oocyte development. Here we show that oocyte-specific deletion of Mfn1, but not Mfn2, prevents the oocyte growth and ovulation due to a block in folliculogenesis. We pinpoint the loss of oocyte growth and ovulation to impaired PI3K-Akt signaling and disrupted oocyte-somatic cell communication. In support, the double loss of Mfn1 and Mfn2 partially rescues the impaired PI3K-Akt signaling and defects in oocyte development secondary to the single loss of Mfn1. Together, this work demonstrates that the mitochondrial function influences the cellular signaling during the oocyte development, and highlights the importance of distinct, nonredundant roles of MFN1 and MFN2 in oogenesis.

Mio-Pliocene piracy, relict landscape and drainage reorganization in the Namcha Barwa syntaxis zone of eastern Himalaya.

The presence of unique elevated low relief relict landscape in the transient Dibang catchment, at the orographic edge of Tibet-Himalaya in the tectonically active Namcha Barwa syntaxial zone, is modelled to understand evolving regional landscape, drainage reorganization and tectonics. This elevated low relief landscape represents a Mio-Pliocene abandoned paleo-channel of the Yarlung river, which was captured by the headward eroding Siang river owing to >600 m base level advantage. The river capture caused isolation of the Dibang river, which evolved as a transient parched catchment since 3-6 Ma after loss of ~17 times drainage area and 4-17 times discharge. The drainage area and discharge gained by the Siang river triggered enormous incision causing aneurysm leading to the accelerated growth of the Tsangpo gorge and affected regional tectonics. This paleo-drainage reorganization is reflected in the Mio-Pliocene sedimentation pattern in the southern Tibet-Himalaya and foreland basins.

Air travel and pulmonary embolism: "economy class syndrome".

Air travel is implicated as a predisposing factor for thromboembolism, which at times can have catastrophic consequences. We present three cases who developed deep vein thrombosis (DVT) and subsequent pulmonary thromboembolism (PTE) after transatlantic air travel.

12 lead ECG in the detection of left main coronary artery occlusion during acute coronary syndromes.

A careful evaluation of the 12 Lead surface ECG may help detect Left Main Coronary artery (LMCA) occlusion. Since LMCA occlusion can cause rapid hemodynamic and electrical deterioration, early identification may help the treating team to plan out timely revascularization. We describe a 61 years old male who presented with acute anterior wall myocardial infarction and where LMCA occlusion was suspected on the basis of surface ECG. The diagnostic criteria available are discussed.

Interventional therapy for multiple cardiac defects.

We describe a patient with a rare combination of coronary artery disease and congenital heart disease. The patient underwent successful complex and multivessel coronary angioplasty, balloon pulmonary valvuloplasty by the Inoue balloon and transcatheter closure of an atrial septal defect in a staged manner. It is technically feasible and safe to perform multiple interventions as an alternative to open heart surgery.