The mineralogy of Vesta, based on data obtained by the Dawn spacecraft's visible and infrared spectrometer, is consistent with howardite-eucrite-diogenite meteorites. There are considerable regional and local variations across the asteroid: Spectrally distinct regions include the south-polar Rheasilvia basin, which displays a higher diogenitic component, and equatorial regions, which show a higher eucritic component. The lithologic distribution indicates a deeper diogenitic crust, exposed after excavation by the impact that formed Rheasilvia, and an upper eucritic crust. Evidence for mineralogical stratigraphic layering is observed on crater walls and in ejecta. This is broadly consistent with magma-ocean models, but spectral variability highlights local variations, which suggests that the crust can be a complex assemblage of eucritic basalts and pyroxene cumulates. Overall, Vesta mineralogy indicates a complex magmatic evolution that led to a differentiated crust and mantle.

Dawn's global mapping of Vesta reveals that its observed south polar depression is composed of two overlapping giant impact features. These large basins provide exceptional windows into impact processes at planetary scales. The youngest, Rheasilvia, is 500 kilometers wide and 19 kilometers deep and finds its nearest morphologic analog among large basins on low-gravity icy satellites. Extensive ejecta deposits occur, but impact melt volume is low, exposing an unusual spiral fracture pattern that is likely related to faulting during uplift and convergence of the basin floor. Rheasilvia obliterated half of another 400-kilometer-wide impact basin, Veneneia. Both basins are unexpectedly young, roughly 1 to 2 billion years, and their formation substantially reset Vestan geology and excavated sufficient volumes of older compositionally heterogeneous crustal material to have created the Vestoids and howardite-eucrite-diogenite meteorites.

Vesta is a large differentiated rocky body in the main asteroid belt that accreted within the first few million years after the formation of the earliest solar system solids. The Dawn spacecraft extensively imaged Vesta's surface, revealing a collision-dominated history. Results show that Vesta's cratering record has a strong north-south dichotomy. Vesta's northern heavily cratered terrains retain much of their earliest history. The southern hemisphere was reset, however, by two major collisions in more recent times. We estimate that the youngest of these impact structures, about 500 kilometers across, formed about 1 billion years ago, in agreement with estimates of Vesta asteroid family age based on dynamical and collisional constraints, supporting the notion that the Vesta asteroid family was formed during this event.

Vesta's surface is characterized by abundant impact craters, some with preserved ejecta blankets, large troughs extending around the equatorial region, enigmatic dark material, and widespread mass wasting, but as yet an absence of volcanic features. Abundant steep slopes indicate that impact-generated surface regolith is underlain by bedrock. Dawn observations confirm the large impact basin (Rheasilvia) at Vesta's south pole and reveal evidence for an earlier, underlying large basin (Veneneia). Vesta's geology displays morphological features characteristic of the Moon and terrestrial planets as well as those of other asteroids, underscoring Vesta's unique role as a transitional solar system body.

PURPOSE: Clinical features of symptomatic uncomplicated diverticular disease are poorly investigated. Abdominal symptoms may be similar to those of irritable bowel syndrome. This survey aimed to assess clinical features associated with symptomatic uncomplicated diverticular disease. METHODS: This multicenter survey included consecutive outpatients with symptomatic uncomplicated diverticular disease to whom a detailed clinical questionnaire regarding demographic, lifestyle, and clinical features was administered. Diagnosis was based on the presence of diverticula and abdominal pain/discomfort. Irritable bowel syndrome and functional dyspepsia were assessed according to Rome III criteria. RESULTS: A total of 598 patients (50 % female, age 69 years), 71 % with newly diagnosed symptomatic uncomplicated diverticular disease and 29 % with history of colonic diverticula, were recruited. Diverticula were localized in the left colon in 78 % of the patients. Recurrent short-lived abdominal pain (<24 h) was present in 70 %(relieved by evacuation in 73 %), prolonged abdominal pain (>24 h) in 27 %, and recurrent abdominal bloating in 61 % of the patients. Normal, loose, or hard stools were reported by 58, 29, and 13 % of patients, respectively. Irritable bowel syndrome (IBS)-like and functional dyspepsia-like symptoms were recorded in 59 and 7 % of patients, respectively. IBS-like symptoms (odds ratio, 4.3) were associated in patients with prolonged abdominal pain. CONCLUSIONS: Symptomatic uncomplicated diverticular disease is associated with a gender ratio of 1:1 and an unspecific clinical picture mainly characterized by normal stools, short-lived abdominal pain, abdominal bloating, IBS-like symptoms, while functional dyspepsia-like symptoms are not commonly present. These findings suggest that symptomatic uncomplicated diverticular disease often shows similar findings rather than overlaps IBS.

Ca(2+) transfer from endoplasmic reticulum (ER) to mitochondria can trigger apoptotic pathways by inducing release of mitochondrial pro-apoptotic factors. Three different types of inositol 1,4,5-trisphosphate receptor (IP(3)R) serve to discharge Ca(2+) from ER, but possess some peculiarities, especially in apoptosis induction. The anti-apoptotic protein Akt can phosphorylate all IP(3)R isoforms and protect cells from apoptosis, reducing ER Ca(2+) release. However, it has not been elucidated which IP(3)R subtypes mediate these effects. Here, we show that Akt activation in COS7 cells, which lack of IP(3)R I, strongly suppresses IP(3)-mediated Ca(2+) release and apoptosis. Conversely, in SH-SY 5Y cells, which are type III-deficient, Akt is unable to modulate ER Ca(2+) flux, losing its anti-apoptotic activity. In SH-SY 5Y-expressing subtype III, Akt recovers its protective function on cell death, by reduction of Ca(2+) release. Moreover, regulating Ca(2+) flux to mitochondria, Akt maintains the mitochondrial integrity and delays the trigger of apoptosis, in a type III-dependent mechanism. These results demonstrate a specific activity of Akt on IP(3)R III, leading to diminished Ca(2+) transfer to mitochondria and protection from apoptosis, suggesting an additional level of cell death regulation mediated by Akt.

Since 1929, when it was discovered that ATP is a substrate for muscle contraction, the knowledge about this purine nucleotide has been greatly expanded. Many aspects of cell metabolism revolve around ATP production and consumption. It is important to understand the concepts of glucose and oxygen consumption in aerobic and anaerobic life and to link bioenergetics with the vast amount of reactions occurring within cells. ATP is universally seen as the energy exchange factor that connects anabolism and catabolism but also fuels processes such as motile contraction, phosphorylations, and active transport. It is also a signalling molecule in the purinergic signalling mechanisms. In this review, we will discuss all the main mechanisms of ATP production linked to ADP phosphorylation as well the regulation of these mechanisms during stress conditions and in connection with calcium signalling events. Recent advances regarding ATP storage and its special significance for purinergic signalling will also be reviewed.

Mitochondria are key decoding stations of the apoptotic process. In support of this view, a large body of experimental evidence has unambiguously revealed that, in addition to the well-established function of producing most of the cellular ATP, mitochondria play a fundamental role in triggering apoptotic cell death. Various apoptotic stimuli cause the release of specific mitochondrial pro-apoptotic factors into the cytosol. The molecular mechanism of this release is still controversial, but there is no doubt that mitochondrial calcium (Ca(2+)) overload is one of the pro-apoptotic ways to induce the swelling of mitochondria, with perturbation or rupture of the outer membrane, and in turn the release of mitochondrial apoptotic factors into the cytosol. Here, we review as different proteins that participate in mitochondrial Ca(2+) homeostasis and in turn modulate the effectiveness of Ca(2+)-dependent apoptotic stimuli. Strikingly, the final outcome at the cellular level is similar, albeit through completely different molecular mechanisms: a reduced mitochondrial Ca(2+) overload upon pro-apoptotic stimuli that dramatically blunts the apoptotic response.

The tight interplay between endoplasmic reticulum (ER) and mitochondria is a key determinant of cell function and survival through the control of intracellular calcium (Ca(2+)) signaling. The specific sites of physical association between ER and mitochondria are known as mitochondria-associated membranes (MAMs). It has recently become clear that MAMs are crucial for highly efficient transmission of Ca(2+) from the ER to mitochondria, thus controlling fundamental processes involved in energy production and also determining cell fate by triggering or preventing apoptosis. In this contribution, we summarize the main features of the Ca(2+)-signaling toolkit, covering also the latest breakthroughs in the field, such as the identification of novel candidate proteins implicated in mitochondrial Ca(2+) transport and the recent direct characterization of the high-Ca(2+) microdomains between ER and mitochondria. We review the main functions of these two organelles, with special emphasis on Ca(2+) handling and on the structural and molecular foundations of the signaling contacts between them. Additionally, we provide important examples of the physiopathological role of this cross-talk, briefly describing the key role played by MAMs proteins in many diseases, and shedding light on the essential role of mitochondria-ER interactions in the maintenance of cellular homeostasis and the determination of cell fate.

BACKGROUND: PancPRO is a computer program that estimates the risk of pancreatic cancer for asymptomatic individuals based on a genetic model of susceptibility and the familial incidence of cancer. AIM: To evaluate the distribution of the familial risk in a series of incident cases of pancreatic adenocarcinoma. MATERIALS AND METHODS: The lifetime risk of pancreatic cancer was calculated by PancPro for a hypothetical 40-year-old son of 570 consecutive probands with pancreatic cancer. RESULTS: The 570 risk values were included between 1% and 13%. The distribution was bimodal, with the antimode located at risk=7.5%. Considering a 10-fold risk over the general population as a threshold for including a subject in a surveillance program, 19 families (3.3%) would be selected, totalling 92 first-degree relatives with age >40 years. CONCLUSIONS: PancPro is a valid instrument to rank families based on risk of pancreatic cancer.