cAMP Pulsing of Denuded Mouse Oocytes Increases Meiotic Resumption Via Activation of AMP-activated Protein Kinase

cAMP plays a critical role in the control of oocyte maturation, as a high level of cAMP maintains oocyte arrest at the first meiotic prophase. Yet this study shows that pulsing meiotically arrested denuded oocytes (DO) with cAMP induces oocyte maturation through the activation of AMP-activated protein kinase (PRKA). Short-term (3 h) pulsing of meiotically arrested oocytes with forskolin, an adenyl cyclase (AC) activator, increased oocyte cAMP, led to elevated AMP, and induced oocyte meiotic resumption compared to oocytes continuously cultured in the control medium with or without forskolin. Western analysis showed that germinal vesicle (GV)-stage oocytes after forskolin pulsing contained increased levels of phospho-acetyl CoA carboxylase (pACACA), a primary substrate of PRKA. Pulsing oocytes with the phosphodiesterase (PDE)-sensitive cAMP analog, 8-bromo-cAMP (8-Br-cAMP), also increased pACACA and pPRKA levels in GV-stage oocytes and induced oocyte meiotic resumption. Moreover, the PRKA inhibitors, compound C and araA, prevented 8-Br-cAMP pulsing-induced maturation. The lack of effect on meiotic induction and PRKA activation when oocytes were pulsed with the PDE-resistant activators of cAMP-dependent protein kinase, Sp-cAMP-AM and Sp-5,6-DCI-cBIMPS, suggests that cAMP degradation is required for pulsing-induced maturation. Pulsing oocytes with the exchange protein directly activated by cAMP (Epac)-specific activator, 8-CPT-2′-O-Me-cAMP, had no stimulatory effect on oocyte maturation, suggesting Epac is not involved in the pulsing-induced maturation. Taken together, these data support the idea that a transient increase in oocyte cAMP can induce meiotic resumption via activation of PRKA

Income Smoothing over the Business Cycle: Changes in Banks’ Coordinated Management of Provisions for Loan Losses and Loan Charge-offs from the Pre-1990 Bust to the 1990s Boom

We provide evidence that banks smooth income by managing provisions for loan losses and loan charge-offs in a coordinated fashion that varies across the bust and boom phases of the business cycle and across homogeneous and heterogeneous loan types. In particular, during the 1990s boom, we predict and find that banks accelerated provisioning for loan losses and made this less obvious by accelerating loan charge-offs, especially for homogenous loans for which charge-offs are determined using number-of-days-past-due rules. We also provide evidence that the valuation implications of banks’ provisions for loan losses and loan charge-offs vary across the phases of the business cycle and loan types reflecting the effect of these factors on banks’ income smoothing. In particular, during the 1990s boom, we predict and find that charge-offs of homogenous loans have a positive association with current returns and future cash flows, because these charge-offs are recorded primarily by healthy banks with good future prospects reducing over-stated allowances for loan losses. We also predict and find that these charge-offs have a positive association with future returns that is explained by their positive association with future net income and recoveries. Our results are consistent with the market only partially appreciating healthy banks’ overstatement of charge-offs of homogeneous loans based on number-of-days-past-due rules during the 1990s boom, because of the perceived non-discretionary nature of these charge-offs

Palladium-Catalyzed Hydroxylation of Aryl and Heteroaryl Halides Enabled by the Use of a Palladacycle Precatalyst

A method for the hydroxylation of aryl and heteroaryl halides, promoted by a catalyst based on a biarylphosphine ligand tBuBrettPhos (L5) and its corresponding palladium precatalyst (1), is described. The reactions allow the cross-coupling of both potassium and cesium hydroxides with (hetero)aryl halides to afford a variety of phenols and hydroxylated heteroarenes in high to excellent yield.National Institutes of Health (U.S.) (GM58160)Croucher Foundation (Postdoctoral Fellowship

Association Between Blood Pressure and Adverse Renal Events in Type 1 Diabetes.

ObjectiveTo compare different blood pressure (BP) levels in their association with the risk of renal outcomes in type 1 diabetes and to determine whether an intensive glycemic control strategy modifies this association.Research design and methodsWe included 1,441 participants with type 1 diabetes between the ages of 13 and 39 years who had previously been randomized to receive intensive versus conventional glycemic control in the Diabetes Control and Complications Trial (DCCT). The exposures of interest were time-updated systolic BP (SBP) and diastolic BP (DBP) categories. Outcomes included macroalbuminuria (>300 mg/24 h) or stage III chronic kidney disease (CKD) (sustained estimated glomerular filtration rate <60 mL/min/1.73 m2).ResultsDuring a median follow-up time of 24 years, there were 84 cases of stage III CKD and 169 cases of macroalbuminuria. In adjusted models, SBP in the <120 mmHg range was associated with a 0.59 times higher risk of macroalbuminuria (95% CI 0.37-0.95) and a 0.32 times higher risk of stage III CKD (95% CI 0.14-0.75) compared with SBPs between 130 and 140 mmHg. DBP in the <70 mmHg range were associated with a 0.73 times higher risk of macroalbuminuria (95% CI 0.44-1.18) and a 0.47 times higher risk of stage III CKD (95% CI 0.21-1.05) compared with DBPs between 80 and 90 mmHg. No interaction was noted between BP and prior DCCT-assigned glycemic control strategy (all P > 0.05).ConclusionsA lower BP (<120/70 mmHg) was associated with a substantially lower risk of adverse renal outcomes, regardless of the prior assigned glycemic control strategy. Interventional trials may be useful to help determine whether the currently recommended BP target of 140/90 mmHg may be too high for optimal renal protection in type 1 diabetes

Education sector response to early and unintended pregnancy: A policy dialogue in Homa Bay County, Kenya

In collaboration with the Strengthening Evidence for Programming on Unintended Pregnancy (STEP UP) Research Programme Consortium, the Population Council implemented a project to increase the demand for secondary school education in Homa Bay County, Kenya—an area characterized by high, unintended teenage pregnancy and female school drop-out rates. To foster awareness of the school re-entry policy, the Population Council collaborated with the Homa Bay County Department of Education (Ministry of Education) to convene a policy dialogue for all principals of public, day, girls-only, and co-educational secondary schools in the area. The policy dialogue helped to create visibility around the issue of unintended pregnancy in schools and the need for a clear, strong education sector response to it. Additionally, the meeting deliberations underscored the need to update current policies based on issues emerging from the dialogue. Lessons learned from the policy dialogue will be incorporated into future interventions under the project

Shares in the EMCA : the time is ripe for true no par value shares in the EU, and the 2nd directive is not an obstacle

The most interesting proposal in the draft European Model Companies Act ( EMCA) concerning shares and the focus of this Article is the recommendation to introduce true no par value shares, as they have been in use in the US for many years and were introduced in Australia, New Zealand but also Finland more recently. Contrary to what has often been assumed, the 2nd EU Company Law Directive does not preclude no par value shares. There is nothing in the wording of the Directive to suggest otherwise, and the reference in the Directive to shares without a nominal value is a reference to Belgian law, which has allowed true no par value shares in all but name since at least 1913. EU member states could therefore introduce such shares even for public companies. True no par value shares offer a far more flexible framework in case of capital increases or mergers, but since under a no par value system there is no link between par value and shareholder rights, additional disclosure about these rights might be warranted under a no par value system. Traditional par value shares offer no protection to creditors, shareholders or other stakeholders, so that their abolition should not be mourned. The threat of new share issues at an unacceptably high discount is more efficiently countered by disclosure and shareholder decision rights