Circadian disruption negatively affects physiology, posing a global health threat that manifests in proliferative, metabolic, and immune diseases, among others. Because outputs of the circadian clock ...regulate daily fluctuations in the immune response, we determined whether circadian disruption results in tumor-associated immune cell remodeling, facilitating tumor growth. Our findings show that tumor growth rate increased and latency decreased under circadian disruption conditions compared to normal light-dark (LD) schedules in a murine melanoma model. Circadian disruption induced the loss or inversion of daily patterns of M1 (proinflammatory) and M2 (anti-inflammatory) macrophages and cytokine levels in spleen and tumor tissues. Circadian disruption also induced (i) deregulation of rhythmic expression of clock genes and (ii) of cyclin genes in the liver, (iii) increased
levels in the tumor, and (iv) dampened expression of the cell cycle inhibitor
, all of which contribute to a proliferative phenotype.
Abstract
Studying tropical hydroclimate and productivity change in the past is critical for understanding global climate dynamics. Northwest Australia is an ideal location for investigating ...Australian monsoon dynamics, the variability of the Indonesian Throughflow (ITF), and their impact on past productivity and Pacific warm pool evolution, which remain poorly understood during the 40 kyr world in the mid‐early Pleistocene. In this study, we present multi‐proxy records from International Ocean Discovery Program (IODP) Site U1483 in the Timor Sea spanning the last 2,000 ka, including orbitally‐resolved records from the 40 kyr world between 2,000 and 1,300 ka. Our results suggest that northwest Australia underwent a step of increased aridification and that productivity in the Timor Sea declined during the transition from ∼1,700 to ∼1,400 ka. We attribute this aridification to the reduced moisture supply to this region caused by the ITF restriction and warm pool contraction. We ascribe the declined productivity to a decrease in the nutrient supply of the Pacific source water associated with global nutrient redistribution. At orbital timescale, multiple mechanisms, including sea level changes, monsoon, and the Intertropical Convergence Zone (ITCZ) dynamics, and variations in the ITF and Walker circulation could have controlled variations of productivity and terrigenous input in the Timor Sea during the 40 kyr world. Our bulk nitrogen and benthic carbon isotope records suggest a strong coupling to biogeochemical changes in the Pacific during this period. This research contributes to a better understanding of tropical hydroclimate and productivity changes during the 40 kyr world.
Plain Language Summary
The northwest Australian region is located at the southwestern edge of the Indo‐Pacific Warm Pool and experiences a seasonal monsoon climate. Oceanic and climate conditions in this region are also strongly influenced by the Indonesian Throughflow (ITF), which is the only tropical pathway in the modern ocean connecting the Pacific and Indian Oceans and providing the main conduit for the exchange of water, salt, and heat between these oceans. These conditions make northwest Australia a strategic location to explore Australian monsoon dynamics, the variability of the ITF, and the interaction between tropical hydroclimate and productivity in the past. However, these processes are poorly documented during the 40 kyr world in the mid‐early Pleistocene, when glacial‐interglacial cycles mainly varied at the 41 kyr obliquity band. Here, we present multiple‐proxy marine records from a site directly impacted by the ITF and we examine terrigenous input and productivity changes in this region over the last 2,000 kyr. Our results suggest that northwest Australia underwent a step of increased aridification and that productivity in the Timor Sea declined during the transition from ∼1,700 to ∼1,400 ka, due to restriction of the ITF, warm pool contraction, and decreased nutrient supply from the Pacific source water.
Key Points
Northwest Australia underwent aridification from ∼1,700 to 1,400 ka due to restricted Indonesian Throughflow and warm pool contraction
Decreased productivity in the Timor Sea from ∼1,700 to 1,400 ka reflected decreased nutrient supply from Pacific source water
Orbital variation in productivity and terrigenous input in the Timor Sea during the 40 kyr world are driven by multiple mechanisms
The subsurface plumbing system of ancient seeps of hydrocarbon-rich gases and fluids is partially preserved by seep deposits in Miocene rocks of the Coast Ranges and on the seafloor of the Monterey ...Bay region in central California. The fossil seep-related deposits are of two types: authigenic carbonates and intrusions of oil-saturated sandstones. Both types occur in fractured and faulted siliceous mudstone and porcelanite layers of the organic-rich Miocene Santa Cruz Mudstone. They are associated with tectonic structures indicating deformation, and are located in the proximity of faults. The morphology of the seep carbonates is characterized by strong asymmetries and by holes, pipes and other types of fluid conduits with orientations parallel to the directions of the local fracture- and fault-sets, thus suggesting structural control over pathways of fluid migration. The dominant direction of the conduits in the seep carbonates and of the intrusive dikes (northeast–southwest) differs from the dominant orientation of the tectonic structures of the San Andreas Fault System (northwest–southeast). Previous interpretations of these ancient seep-related deposits suggested that lateral changes of the thickness of the Cenozoic marine host sediments favored fluid migration from basin depocenters located offshore toward basin margins. Different driving forces for fluids have been hypothesized including hydrocarbon generation, differential compaction, and tectonic compression. Most of the fossil seeps are located on structural highs of the basement and adjacent to offshore basins that form elongated depressions oriented northwest–southeast. Previously unidentified structures that offset the basement along northeast–southwest trends (cross-setting faults) paralleling the orientations of the conduits of the seep carbonates and the dikes of oil-saturated sandstones were also recognized. Tectonic deformation, block rotations (documented by local clockwise rotations of paleomagnetic directions in the Coastal Ranges) and cross-faults were probably produced during the Late Miocene and Pliocene to accommodate the shear stress between conjugate faults during eastward shifting of the activity of the San Andreas Fault System. Comparison with previous studies on ancient seep deposits, regional geology and offshore tectonic data, suggest that the fluids that sourced the seeps were driven by episodes of inverse tectonics, during which previously extensional depositional basins were involved in episodes of tectonic compression. Tectonic deformation created cross-faults in rotated blocks, which could have acted as important conduits for the flow of hydrocarbon-rich fluids and gases and fostered the injection of liquefied sands.
The spectroscopic characterization of the metal complexes the 5-amidopyridine-8-hydroxyquinoline (HQ′NHCOC
5H
4N) form with M = Be, Zn, Cd, Al, Ga and In is reported. These compounds, M(Q′NHCOC
5H
...4N)
2 (M = Be, Zn, Cd) and M(Q′NHCOC
5H
4N)
3 (M = Al, Ga, In), are highly soluble in DMSO and, in addition, the gallium and indium products dissolve in methyl or ethyl alcohol. These species are very stable in solution and emit in the range 520 (Be)–590 (Ga and In)
nm with photoluminescent quantum yields ranging from 0.010 (Al) to 0.001 (In). Processability and color emission suggest that some of these new materials can be of interest for practical applications in optoelectronic devices.
Objective: (1) To assess cognitive function and cerebral magnetic resonance imaging (MRI) involvement in relapsing-remitting multiple sclerosis; (2) to monitor disease evolution, cognitive ...dysfunction, and cerebral lesion burden over time (mean 8.5 year follow up period); (3) to study the relation between clinical, neuropsychological, and MRI data. On follow up assessment, visual and auditory oddball event related potentials (ERPs) were recorded as psychophysiological evaluation of cognitive status. Correlations between neuropsychological, MRI, and ERP data were also analysed. Methods: Neuropsychological study assessed verbal and non-verbal IQ, deterioration index (DI) from WAIS subtests, conceptual reasoning, attention, verbal and visuospatial short-term and long term memory. MRI assessment detected presence of demyelinating lesions by using a semiquantitative method as well as cortical and subcortical atrophy over time. Results: Attention, short-term and long term visuospatial memory were mildly impaired at baseline and remained unaltered longitudinally. At retesting a significant worsening of verbal long term memory (p=0.023), DI presence (p=0.041) and the increase of supratentorial and subtentorial MRI lesions load (p=0.001) emerged. Expanded disability status scale score correlated significantly with total lesion burden at both evaluations (p=0.043 and p=0.024 respectively). Temporal, occipital, and frontal horn lesions as well as cortical atrophy correlated significantly with attention and memory tests at baseline. Follow up assessment revealed significant correlation between cortical atrophy and attention as well as visuospatial short-term memory; spatial long term memory correlated significantly with lesions in body of lateral ventricle and frontal lobe. ERP study showed P300 latency abnormalities in 75% of patients, involving specifically more visual P300 (58.4 % of cases) than auditory wave (41.6 %). Visual P300 latency and amplitude correlated significantly with DI and auditory P300 latency with frontal horn and brain stem lesions. Conclusions: These findings revealed mild cognitive impairment in MS patients particularly consistent with slowing information processing over time. Increased MRI lesions do not correlate with the clinical course of the disease and cognitive deficit evolution. Thus, cognitive dysfunction could be related to disease peculiarity and not to the time course. Correlations between P300, neuropsychological, and MRI findings provide further information about ERP application to examine cognitive impairment in MS and probably to investigate their neural origin.
Cognitive impairment in multiple sclerosis (MS) has received considerable interest over the last decades. Heterogeneous patterns of cognitive dysfunction have been reported in literature in relation ...to the subtype of the disease and the severity of specific cognitive domains affected. Event related potentials (ERPs), especially P300, have been employed to evaluate the cognitive decline in MS and neurophysiological findings agree with data obtained by neuropsychological testing. The objectivity, the reliability and the easy administration are the main features of ERP technique but more specific attention and memory tasks are needed to enhance the clinical value of the methodology. Moreover, ERP recording has the advantage of being feasible even in severe disabled patients. Finally, longitudinal ERP studies are required to investigate the natural course of cognitive dysfunction in MS, to estimate the prognostic value of subclinical defects in different clinical form of the disease and to evaluate clinical benefits of therapeutic and rehabilitative interventions.
To investigate whether internuclear ophthalmoparesis (INO) due to demyelination of the medial longitudinal fasciculus (MLF) provides a model for studying the poorly understood symptom of fatigue in ...multiple sclerosis (MS). We asked whether repetitive horizontal saccades increased eye movement disconjugacy in patients with MS with INO, but not in healthy subjects.
We compared conjugacy of horizontal saccades in 9 patients with INO (4 bilateral, total 13) and 8 controls during minute 1 and minute 10 of a fatigue test; we measured the ratio of abducting/adducting peak velocity (versional disconjugacy index VDI).
VDI values were greater in patients than controls. During the fatigue test, controls showed no changes of VDI, but patients did (p < 0.005) for 10/13 INOs, with increased ratios in 5 cases and a decrease in the other 5.
Fatigue-induced worsening of conjugacy was observed in milder internuclear ophthalmoparesis (INO), and may reflect deteriorated fidelity of saccadic pulse transmission along demyelinated medial longitudinal fasciculus. Improved conjugacy was observed in the more severe INOs, and may be due to adaptive mechanisms, such as recruitment of vergence to aid gaze shifts. INO may provide an accessible, reductionist model to study how decreased neural transmission influences fatigue in multiple sclerosis, how the brain adapts to it, and whether drugs may prove therapeutic.
Radiolarian-rich sediments dominated pelagic deposition over large portions of the Tethys Ocean during middle to late Jurassic time as shown by extensive bedded chert sequences found in both ...continental margin and ophiolite units of the Mediterranean region. Which paleoceanographic mechanisms and paleotectonic setting favored radiolarian deposition during the Jurassic, and the nature of a Tethys-wide change from biosiliceous to biocalcareous (mainly nannofossil) deposition at the beginning of Cretaceous time, have remained open questions. Previous paleomagnetic analyses of Jurassic red radiolarian cherts in the Italian Apennines indicate that radiolarian deposition occurred at low peri-equatorial latitudes, similar to modern day deposition of radiolarian-rich sediments within equatorial zones of high biologic productivity. To test this result for other sectors of the Mediterranean region, we undertook paleomagnetic study of Mesozoic (mostly middle to upper Jurassic) red radiolarian cherts within the Aegean region on the Peloponnesus and in continental Greece. Sampled units are from the Sub-Pelagonian Zone on the Argolis Peninsula, the Pindos–Olonos Zone on the Koroni Peninsula, near Karpenissi in central Greece, and the Ionian Zone in the Varathi area of northwestern Greece. Thermal demagnetization of samples from all sections removed low-temperature viscous and moderate-temperature overprint magnetizations that fail the available fold tests. At Argolis and Koroni, however, the cherts carry a third high-temperature magnetization that generally exhibits a polarity stratigraphy and passes the available fold tests. We interpret the high-temperature component to be the primary magnetization acquired during chert deposition and early diagenesis. At Kandhia and Koliaky (Argolis), the primary declinations and previous results indicate clockwise vertical-axis rotations of ∼
40° relative to “stable” Europe. Due to ambiguities in hemispheric origin (N or S) and thus paleomagnetic polarity, the observed declinations could indicate either clockwise (CW) or counterclockwise (CCW) vertical-axis rotations. Thus at Adriani (Koroni), the primary declinations indicate either CW or CCW rotations of ∼
95° or ∼
84°, depending on paleomagnetic polarity and age. The primary inclinations for all Peloponnesus sites indicate peri-equatorial paleolatitudes similar to those found for coeval radiolarian cherts exposed in other Mediterranean orogenic belts. Our new paleomagnetic data support the interpretation that Mesozoic radiolarites within the Tethys Ocean were originally deposited along peri-equatorial belts of divergence and high biologic productivity.
Cerebellar pathology commonly shows important motor signs and less evident cognitive dysfunction. The 'cerebellar cognitive affective syndrome' is characterised by impairment on executive function, ...spatial cognition, language and behaviour. We report the case of a man with acute onset of transitory motor features and severe mental disorders. Cranial CT and brain MRI revealed extended cerebellar lesions. Neuropsychological assessment disclosed deficits of attention, executive function and memory. Auditory event-related potentials showed abnormal P300. These data suggest a pure "cerebellar cognitive affective syndrome"and strengthen the hypothesis of cerebellar cognitive function modulation.
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