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The effect of modified equator‐to‐pole temperature gradients on the jet stream by low‐level polar warming and upper‐level tropical warming is not fully understood. We perform aquaplanet simulations to quantify the impact of different sea surface temperature distributions on jet stream strength, large wave amplitudes and extreme waviness. The responses to warming in the waviness metrics Sinuosity Index and Local Wave Activity are sensitive to the latitude range over which they are calculated. Therefore, we use a latitude range that accurately represents the position of the jet. The uniform warming scenario strengthens the jet and reduces large wave amplitudes. Reductions in meridional temperature gradients lead to weakened mid‐latitudinal jet strength and show significant decreases in large wave amplitudes and jet stream waviness. These findings contradict the mechanism that weakened jet streams increase wave amplitudes and extreme jet stream waviness. We conclude that weakened jet streams do not necessarily become wavier. This research letter considers how different patterns of atmospheric warming, like low‐level warming at the poles and at high altitude in the tropics, impact the jet stream, which is a strong “river” of high‐altitude wind. We use numerical model simulations to mimic different scenarios of warming that maintain or reduce the temperature gradient between equator and poles. We find that when an Earth‐like planet completely covered by water warms in specific ways, it strengthens the jet stream when it is warmed uniformly or weakens the jet stream when only mid‐ and high latitudes are warmed. For the simulations with a reduced mid‐latitudinal temperature gradient, the size of largest jet stream waves reduces and makes the extreme waviness episodes less wavy. This research letter conclude that weakened jet streams do not necessarily become wavier, which opposes the popular paradigm that weakened jet streams become wavier due to warming in polar regions. On an aquaplanet, weakened jet streams do not become wavier with reduced temperature gradients due to warming in mid‐ and high latitudesIn reduced temperature gradient simulations, the magnitude of large wave amplitudes and jet stream extreme waviness decrease robustlyThe Sinuosity Indexand the Local Wave Activitywaviness metrics are sensitive to the latitude range over which they are calculated On an aquaplanet, weakened jet streams do not become wavier with reduced temperature gradients due to warming in mid‐ and high latitudes In reduced temperature gradient simulations, the magnitude of large wave amplitudes and jet stream extreme waviness decrease robustly The Sinuosity Indexand the Local Wave Activitywaviness metrics are sensitive to the latitude range over which they are calculated

Insulin and insulin-like growth factors (IGFs) are mitogenic and prosurvival factors to many different cell types, including acute lymphoblastic leukemia (ALL). Circulating IGFs are bound by IGF binding proteins (IGFBPs) that regulate their action. IGFBP7 is an IGFBP-related protein (IGFBP-rP) that in contrast to other IGFBPs/IGFBP-rPs features higher affinity for insulin than IGFs and was shown to bind the IGF1 receptor (IGF1R) as well. The role of IGFBP7 in cancer is controversial: on some tumors, it functions as an oncogene, whereas in others, it functions as a tumor suppressor. In childhood ALL, higher IGFBP7 expression levels were associated with worse prognosis. Here we show that IGFBP7 exerts mitogenic and prosurvival autocrine effects on ALL cells that were dependent on insulin/IGF. IGFBP7 knockdown or antibody-mediated neutralization resulted in significant attenuation of ALL cell viability in vitro and leukemia progression in vivo. IGFBP7 was shown to prolong the surface retention of the IGF1R under insulin/IGF1 stimulation, resulting in sustained IGF1R, insulin receptor substrate 1 (IRS-1), protein kinase B (AKT), and extracellular signal-regulated kinase (ERK) phosphorylation. Conversely, the insulin receptor was readily internalized and dephosphorylated on insulin stimulation, despite IGFBP7 addition. The affinity of homodimeric IGF1R for insulin is reportedly >100 times lower than for IGF1. In the presence of IGFBP7, however, 25 ng/mL insulin resulted in IGF1R activation levels equivalent to that of 5 ng/mL IGF1. In conclusion, IGFBP7 plays an oncogenic role in ALL by promoting the perdurance of IGF1R at the cell surface, prolonging insulin/IGF stimulation. Preclinical data demonstrate that IGFBP7 is a valid target for antibody-based therapeutic interventions in ALL.

ABSTRACTMycobacterium bovisBCG prime DNA (Mycobacterium tuberculosisgenes)-booster vaccinations have been shown to induce greater protection against tuberculosis (TB) than BCG alone. This heterologous prime-boost strategy is perhaps the most realistic vaccination for the future of TB infection control, especially in countries where TB is endemic. Moreover, a prime-boost regimen using biodegradable microspheres seems to be a promising immunization to stimulate a long-lasting immune response. The alanine proline antigen (Apa) is a highly immunogenic glycoprotein secreted by M. tuberculosis. This study investigated the immune protection of Apa DNA vaccine against intratracheal M. tuberculosischallenge in mice on the basis of a heterologous prime-boost regimen. BALB/c mice were subcutaneously primed with BCG and intramuscularly boosted with a single dose of plasmid carrying apaand 6,6'-trehalose dimycolate (TDM) adjuvant, coencapsulated in microspheres (BCG-APA), and were evaluated 30 and 70 days after challenge. This prime-boost strategy (BCG-APA) resulted in a significant reduction in the bacterial load in the lungs, thus leading to better preservation of the lung parenchyma, 70 days postinfection compared to BCG vaccinated mice. The profound effect of this heterologous prime-boost regimen in the experimental model supports its development as a feasible strategy for prevention of TB.

ObjectiveTo compare sexual functioning and distress in women with systemic sclerosis SSc with that in healthy controls and determine the association between disease characteristics and sexual function.MethodsWe conducted a crosssectional study of 69 women with SSc ages 18–60 years and 58 healthy, agematched controls. Assessment included the Female Sexual Function Index FSFI, Female Sexual Distress Scale FSDS, Hospital Anxiety and Depression Scale, Short Form 36 health survey, sociodemographic characteristics, and in patients only, the Health Assessment Questionnaire.ResultsOf 69 eligible patients with SSc, 37 54 responded, in addition to 37 64 of 58 controls. The FSFI total score and the subscale scores for lubrication, orgasm, arousal, and pain were significantly lower and the FSDS scores were significantly higher in patients with SSc. Longer disease duration and higher levels of marital dissatisfaction were significantly associated with low sexual function in patients with SSc. Longer disease duration, more depressive symptoms, and the use of antidepressants were significantly associated with sexual distress. Multivariate analyses indicated that marital distress was the only variable significantly associated with low sexual function in patients with SSc β 0.40, P< 0.05, whereas depression was the only variable significantly associated with sexual distress β 0.32, P< 0.05. The same pattern of associations was found in the healthy control group.ConclusionWomen with SSc reported significantly impaired sexual functioning and more sexual distress then healthy controls. Impaired sexual functioning and sexual distress were associated with marital distress and depressive symptoms. These results indicate that in daily practice, inquiring about sexuality and screening for depressive symptoms is indicated in every patient with SSc, irrespective of their clinical characteristics.

Contrary to the general notion that extratropical cyclones reduce baroclinicity, the baroclinicity is found to be enhanced in the wake of the extreme winter storm Dagmar. Thus, individual storms can increase baroclinicity, yielding a pathway to secondary cyclogenesis and cyclone clustering. We use a recently introduced diagnostic for baroclinicity—the tendency equation for the isentropic slope—and found that strong diabatic heating due to moisture supply from the subtropical Atlantic led to the enhanced baroclinicity in the rear of Dagmar. Storms ensuing Dagmar benefited from this increased baroclinicity. In contrast to previous studies on the mechanisms of cyclone clustering, we only find weak evidence for Rossby wave breaking and thus propose diabatic heating as an alternative pathway to cyclone clustering. Evolution of baroclinicity is investigated using the isentropic slope frameworkIsentropic framework is consistent with traditional energy framework without requiring a separation into mean and perturbationDiabatic heating associated with storm Dagmar yields an increased baroclinicity associated with cyclone clustering