Generalized Killing equations and Taub-NUT spinning space

The generalized Killing equations for the configuration space of spinning particles (spinning space) are analysed. Simple solutions of the homogeneous part of these equations are expressed in terms of Killing-Yano tensors. The general results are applied to the case of the four-dimensional euclidean Taub-NUT manifold.Comment: 10 pages, late

Autophagy and the lysosomal system in cancer

Autophagy and the lysosomal system, together referred to as the autophagolysosomal system, is a cellular quality control network which maintains cellular health and homeostasis by removing cellular waste including protein aggregates, damaged organelles, and invading pathogens. As such, the autophagolysosomal system has roles in a variety of pathophysiological disorders, including cancer, neurological disorders, immune- and inflammation-related diseases, and metabolic alterations, among others. The autophagolysosomal system is controlled by TFEB, a master transcriptional regulator driving the expression of multiple genes, including autophagoly sosomal components. Importantly, Reactive Oxygen Species (ROS) production and control are key aspects of the physiopathological roles of the autophagolysosomal system, and may hold a key for synergistic therapeutic interventions. In this study, we reviewed our current knowledge on the biology and physiopathology of the autophagolysosomal system, and its potential for therapeutic intervention in cancer

How Do Older Patients with End-Stage Osteoarthritis of the Hip Eat Prior to Hip Replacement? A Preliminary Snapshot That Highlights a Poor Diet

Diet quantity and quality in older adults is critical for the proper functioning of the musculoskeletal system. In view of hip surgery, old patients should consume 1.2–1.5 g of proteins and 27–30 kcal per kilo of body weight daily, and adhere to healthy eating habits. In this analytical study, we studied diet quantity and quality in relation to the clinical chemistry and functional status of 57 older adults undergoing elective hip replacement. Nine in ten patients did not meet suggested protein and energy intakes and only one in ten patients exhibited high adherence to the Mediterranean diet. Legume consumption adjusted for sex, age, body mass index, and health status successfully forecasted haemoglobin levels (p < 0.05), and patients regularly consuming olive oil reported minor hip disability compared to those using it less frequently (p < 0.05). Patients who reported daily ingestion of <1 serving of meat versus those consuming >1.5 servings had greater cumulative comorbidity (p < 0.05), with meat consumption independently predicting walking ability, mobility, and balance in the fully adjusted model (p < 0.01). In conclusion, our patients seem to eat poorly. There is room for improvement in pre-operative pathways to make older adults eat better, but there is a need to plan an interventional study to fully understand the cause–effect of a dietary pattern or specific food in enhancing recovery after surgery

Strontium isotopic geochemistry of Pan-African/Brasiliano rocks, Chapada copper deposit, Goiás, Brazil

Das Trägergestein der Chapada Kupferlagerstätte in Goiás ist in metamorpher Hoch-Amphibolitfazies ausgebildet. Gesamtgesteins- und individuelle Mineral Rb-Sr-Isochronen mit einem 87 Sr/ 86 Sr-Initialwert (I) von 0,70414±0.00005 ergeben für die Kristallisation der Vulkanite und Magmatite, die die Metamorphose vordatieren, ein Alter von 561±9 Mio Jahre. Die Datierung der Metamorphose während der panafrikanisch/brasilianischen Orogenese (700 bis 450 Mio Jahre) ergibt 532±1 Mio Jahre. Das Mineral-Isochronenalter eines Dioritkörpers porphyrischen Gefüges, der in die Schiefer intrudierte, beträgt 534±16 Mio Jahre (I=0,70415 ±0,00004). Das Ergebnis niedriger Initial-Werte dieser Isochronen ergibt für die Schiefer bei Chapada ein Ausgangs-Material im Bereich des oberen Mantels oder der tieferen Kruste; diese Ausgangswerte sind charakteristisch für magmatische Tätigkeit in Verbindung mit Inselbögen. Das unterkambrische Alter des Trägergesteins bei Chapada steht im Widerspruch zu dem bisher angenommenen mittelproterozoischen Alter und ist ein Hinweis auf eine mögliche Phase intensiverer pan-afrikanisch/brasilianischer magmatischer Aktivität in Zentral-Brasilien als ursprünglich angenommen wurde. Whole rock and mineral Rb-Sr isochrons from the upper amphibolite grade metamorphic host rocks of the Chapada copper deposit in Goiás, Brazil, yield an age of 561±9 Ma, with a 87 Sr/ 86 Sr initial (I) of 0.70414±0.00005, for the crystallization of pre-metamorphic volcanic and igneous rocks and 532 ±1 Ma for their metamorphism during the Pan-African/Brasiliano orogeny (700-450 Ma). A porphyritic diorite stock which intruded the host schists yields a mineral isochron age of 534±16 Ma (I=0.70415±0.00004). The low I values determined from these isochrons suggest that the host schists at Chapada were derived from upper mantle or lower crust material and are characteristic of magmatic products associated with island arcs. The Early Cambrian age of the host rocks at Chapada contradicts the previously assigned mid-Proterozoic age and suggests that Pan-African/Brasiliano magmatic activity may have been more extensive in central Brazil than previously thought. Les roches qui contiennent le gisement de cuivre de Chapada (Goias, Brésil) sont des schistes cristallins appartenent au facies dupérieur des amphibolites. Dans des volcanites et des roches orthomagmatiques appartenant à cet ensemble, des isochrones Rb-Sr sur roches totales et sur minéraux donnent un âge de 561±9 Ma avec un rapport initial de 0,70414±0,00005 pour la cristallisation pré-métamorphique et un âge de 532±1 Ma pour le métamorphisme, lié à l'orogenèse pan-africaine / brésilienne. Un pluton de diorite porphyrique, qui intrude les schistes cristallins donne, par isochrone sur minéraux, un âge de 534±16 Ma (rapport initial de 0,70415±0,00004). Les valeurs basses des rapports initiaux de ces diverses roches suggèrent que les schistes de Chapada sont dérivés de matériaux mantelliques ou crustaux profonds et présentent les caractères des produits magmatiques associés aux arcs insulaires. Leur âge éo-cambrien, en contradiction avec l'âge mésoprotérozoïque admis jusqu'ici, permet de penser que l'activité magmatique pan-africaine/brésilienne dans le centre du Brésil a été plus intense que ce qu'on croyait jusqu'ici. Вмещающие породы зал ежи меди Chapada в Goiбs представляют собой а мфиболитовую фацию в ысшей степени метаморфизм а. Цельная порода и отд ельные минералы дают для кри сталлизации вулкани тов и магматитов до метаморфизма нача льное значение соотн ошения стронция в 0,70414±0,00005, что раз решает принять их возраст в 561± 9 Мио лет, а возраст мет аморфизма в 532±1 Мио, т. е. отнести его к периоду панафриканского -бра зильского орогенеза / 700 до 450 Мио /. При определении в озраста минералов из диоритных тел порфиритовых тек стур, интрудированны х в сланец, получили дат ы в 534±16 Мио лет / 1 = 0,70415 = 0,00004 /. Такое низкое значе ние исходных величин соотношения изотопов разрешает п редполагать, что материал для Chapada при несен был из мантии, или глубинных регион ов коры. Эти исходные з начения характерны для магма тической деятельнос ти типа островных дуг. Во зраст вмещающих поро д считают средне-протерозойск им; это стоит в противо речии с новейшими данными, п о которым он может быт ь только нижнекембрий ским. Это также указыв ает на то, что фаза пан-африка нско-бразильской маг матической активности в централ ьной Бразилии протек ала, возможно, гораздо инт енсивнее, чем принима ли это до сих пор.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47849/1/531_2005_Article_BF01830182.pd

Early Immunotherapy and Longer Corticosteroid Treatment Are Associated With Lower Risk of Relapsing Disease Course in Pediatric MOGAD

Background and Objectives We sought to identify early factors associated with relapse and outcome in paediatric-onset myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD). Methods In a multicenter retrospective cohort of pediatric MOGAD (≤18 years), onset features and treatment were compared in patients with monophasic vs relapsing disease (including cases with follow-up ≥12 months after onset or relapse at any time) and in patients with final Expanded Disability Status Scale (EDSS) 0 vs ≥1 at last follow-up (including cases with followup >3 months after last event or EDSS0 at any time). Multivariable logistic regression models were used to evaluate factors associated with relapsing disease course and EDSS ≥ 1 at final follow-up. Results Seventy-five children were included (median onset age 7 years; median 30 months of follow-up). Presentation with acute disseminated encephalomyelitis was more frequent in children aged 8 years or younger (66.7%, 28/42) than in older patients (30.3%, 10/33) (p = 0.002), whereas presentation with optic neuritis was more common in children older than 8 years (57.6%, 19/33) than in younger patients (21.4%, 9/42) (p = 0.001). 40.0% (26/65) of patients relapsed. Time to first relapse was longer in children aged 8 years or younger than in older patients (median 18 vs 4 months) (p = 0.013). Factors at first event independently associated with lower risk of relapsing disease course were immunotherapy <7 days from onset (6.7-fold reduced odds of relapsing course, OR 0.15, 95% CI 0.03–0.61, p = 0.009), corticosteroid treatment for ≥5 weeks (6.7-fold reduced odds of relapse, OR 0.15, 95% CI 0.03–0.80, p = 0.026), and abnormal optic nerves on onset MRI (12.5-fold reduced odds of relapse, OR 0.08, 95% CI 0.01–0.50, p = 0.007). 21.1% (15/71) had EDSS ≥ 1 at final follow-up. Patients with a relapsing course had a higher proportion of final EDSS ≥ 1 (37.5%, 9/24) than children with monophasic disease (12.8%, 5/39) (p = 0.022, univariate analysis). Each 1-point increment in worst EDSS at onset was independently associated with 6.7-fold increased odds of final EDSS ≥ 1 (OR 6.65, 95% CI 1.33–33.26, p = 0.021). Discussion At first attack of pediatric MOGAD, early immunotherapy, longer duration of corticosteroid treatment, and abnormal optic nerves on MRI seem associated with lower risk of relapse, whereas higher disease severity is associated with greater risk of final disability (EDSS ≥ 1)

Functional interplay between p63 and p53 controls RUNX1 function in the transition from proliferation to differentiation in human keratinocytes

The interfollicular epidermis is continuously renewed, thanks to a regulated balance between proliferation and differentiation. The ΔNp63 transcription factor has a key role in the control of this process. It has been shown that ΔNp63 directly regulates Runt-related transcription factor 1 (RUNX1) transcription factor expression in mouse keratinocytes. The present study showed for the first time that RUNX1 is expressed in normal human interfollicular epidermis and that its expression is tightly regulated during the transition from proliferation to differentiation. It demonstrated that ΔNp63 directly binds two different RUNX1 regulatory DNA sequences and modulates RUNX1 expression differentially in proliferative or differentiated human keratinocytes. It also showed that the regulation of RUNX1 expression by ΔNp63 is dependent on p53 and that this coregulation relies on differential binding and activation of RUNX1 regulatory sequences by ΔNp63 and p53. We also found that RUNX1 inhibits keratinocyte proliferation and activates directly the expression of KRT1, a critical actor in early keratinocyte differentiation. Finally, we described that RUNX1 expression, similar to ΔNp63 and p53, was strongly expressed and downregulated in basal cell carcinomas and squamous cell carcinomas respectively. Taken together, these data shed light on the importance of tight control of the functional interplay between ΔNp63 and p53 in regulating RUNX1 transcription factor expression for proper regulation of interfollicular epidermal homeostasis