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Sedimentological, paleobiological, mineralogical, and geochemical analyses of a sediment core retrieved on the seafront of Cartagena Bay were performed after high-resolution sampling. A wide series of dates obtained through radiocarbon and amino acid racemization proved that the Holocene record on the analyzed core began at ca. 7300 yr cal BP. Reinterpretation of the marine seismic profiles indicated that the beginning of this transgression was channeled along erosive paleochannels excavated on a coastal plain of, at least, MIS5c age. The Holocene paleoenvironmental evolution consisted of a first period marked by marine conditions with strong inputs from a fan delta linked to the reorganized fluvial network that occurred after the sudden rise of the base level, which caused a growing sedimentary prism. Later, the full marine environment was reflected in the development of a Posidonia - Cymodocea meadow hosting a rich biodiversity of marine species (mollusks, foraminifera, ostracoda). Around 3800 yr cal BP, the area underwent a profound change and a silting process started to alter the conditions, turning the area into a paucispecific brackish marsh environment in which mud deposition was dominant. Since Carthaginian times, arrangement works locally affected the record, allowing the arrival of some marine species due to port work (dredging) undertaken to gain depth and showing anthropic influence. [ABSTRACT FROM AUTHOR]

At the northern tip of the Betic realm (SE Iberian Peninsula), some troughs (synclines) and elevations (anticlines) alternate, marking the present-day coastal lobed morphology of cape-bounded bays, where subsidence and uplift conditions prevailed, respectively. In this study, we were able to establish a clear coastal evolution. To this end, we considered the sedimentological and palaeoenvironmental conditions, the palaeogeographical reconstruction, and recent tectonics until Middle Pleistocene times (MIS 5) through the interpretation of onshore cores, raised marine deposits and geophysical profiles. In this regard, as reflected by both onshore and offshore information, there seems to be a stratigraphical gap from the end of the Pliocene to MIS 15 (Middle Pleistocene). In areas under uplift conditions, linked to tardive Alpine tectonics, the deposits of ancient shorelines and raised beaches were located at different post-depositional elevations, which were dated from odd MIS 15 to MIS 5 using amino acid racemization. Only deposits aged MIS 7 and MIS 5 are roughly at the present-day sea level or some meters above. In the troughs, which remain mostly as lagoons and salt marshes, subsidence did not allow the sedimentary record to be discerned. However, many borehole cores were recovered, attesting lagoonal, marsh, sabkha, or alluvial environmental conditions, which were usually unconnected from the sea. Micropaleontological and amino acid racemization dating revealed these cores to be of MIS15 to MIS5 age. Offshore seismic research revealed five erosive-bounded deposits that are stacked accretionary prisms corresponding to highstands between odd MIS 15 and MIS 5. In contrast, even MISs can be correlated to the erosive horizons that separated the seismic units, reflecting lowstands. In this regard, some bars, at a range of distances from the present-day coastline, protected wetlands from marine influence, allowing the development of diverse sub-environments under changing paleogeographical and paleoclimatological conditions. • Deposits of ancient shorelines and raised beaches were AAR dated from odd MIS 15 to 5. • MIS 7 & MIS 5 deposits are roughly at the present-day sea level or some meters above. • Ancient bars protected wetlands from marine influence allowing some sub-environments. • Offshore erosive-bounded deposits (stacked accretionary prisms) ensued in highstands. • Subsidence and uplift prevailed during Quaternary in the Iberian Mediterranean realm. [ABSTRACT FROM AUTHOR]

Here we reconstructed the evolution of the Mazarrón Basin during the Pleistocene and Holocene. In this regard, we studied 9 cores with the aim to: 1) define a chronological framework; 2) obtain data on the palaeoenvironment; and 3) establish the relationship with recent tectonics. A total of 158 samples were recovered for amino acid racemization (AAR) dating, 4 for radiocarbon dating (14C), and 332 for sedimentological and palaeontological determination, and 110 for determination of the mineralogical content. These approaches allowed us to elucidate the evolutionary phases of the palaeo-landscape of the Mazarrón Basin, a fault-controlled graben affected by diverse faults, mainly those of Las Moreras and Rella. The ages of the records and the facies correlation indicate that Las Moreras Fault controlled sedimentation during Marine Isotope Stage (MIS) 7, whereas the Rella Fault was strongly active during the Middle Holocene. During MIS7, a brackish lagoon developed in the western area, overlying alluvial fan deposits. Later, the area was uplifted, thereby becoming exposed to erosion. The activity of the Rella Fault allowed sedimentation in the western part of the Mazarrón Basin during the Middle Holocene, while in the Upper Holocene sedimentation occurred in the eastern part. The Holocene transgression was reflected in a temporarily floodable marsh in the hinterland, with changing salinity conditions, from brackish to euhaline waters. Along the sea front, the marine influence was evident but not dominant. Thus, the Mazarrón Basin during the Holocene was brackish to highly euhaline, with variable biological diversity linked to a narrow and probably discontinuous communication with the sea, with restricted circulation and long flushing times, which was reflected by the significant presence of halite. The record ended with recent alluvial/anthropic sediments. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 10-year-old autism spectrum disorder (ASD) patient with paternally inherited Contactin-6 (CNTN6) protein. Topics discussed include the behavioral symptoms presented by the patient such as aggression and ritualized activities which confirmed ASD at the age of three, results of the genomic scan performed by whole-exome sequencing (WES), and the characteristics of the additional single-nucleotide variants observed in the patient.

Atmospheric concentrations of 18 polycyclic aromatic hydrocarbons (PAHs) were measured in a rural area in northern Spain. Both the gas phase and particulate fraction were determined to evaluate the types and abundance of PAHs taken up by vegetation and the historical record of PAH deposition in an ombrotrophic peatland over the last 300 years. The total atmospheric PAH concentration was ca. 2.5 ng m−3, a value that is slightly lower value than those found in other rural areas, consistent with those of remote areas (Pyrenees, Alps, and Caledonian Mountains), and much lower than those recorded in urban areas. The particulate fraction showed a greater content of high molecular weight PAHs, whereas the gas phase was enriched in low molecular weight homologues. The concentration of total PAHs in the gas phase was higher than that in the particulate fraction (ca. 80%) and similar to that found in other localities in remote areas. PAHs showed seasonal variability. In this regard, the highest concentrations in the gas phase occurred in winter and autumn, whereas in the particulate fraction they were found in winter and spring. Of note, the concentrations of PAHs increased in the particulate fraction during the years in which fires occurred. The PAH content in peat-forming plants in this area showed a similar distribution to that of the gas phase. The historical record of the depositional fluxes of PAHs in an ombrotrophic peatland in the study area, which was dated radiometrically, allowed to reconstruct the changes in pollutant content between 1775 and the present. In general, the PAHs detected were of pyrogenic origin (fossil fuels and wood combustion). The concentrations of these pollutants increased from uniform background levels at the turn of the second half of the 19th century, which were linked to industrial development, to maximum values during the first half of the 20th century until the beginning of the 21st century, when the extraction and combustion of coal was extensive close to the study area. In contrast, in the uppermost part of the record, PAH concentrations decreased. This reduction is attributed to the implementation of environmental policies, although the concentrations of these pollutants were still greater than during the preindustrial period. To gain a detailed understanding of the deposition and evolution of PAHs in the study area, here it is reported on a new method that integrates current atmospheric data on PAHs with information on their accumulation in plants and the historical peat record of a rural area in Spain. The methodology described herein could be applied to other scenarios in the context of PAH pollution. • The molecular ratios for the PAHs found in Las Conchas mire suggest a pyrogenic fingerprint. • Consistent concentrations of PAHs from atmospheric, living plants and peat record are found. • Particulate fraction showed a greater content of high molecular weight PAHs. • Gas phase was enriched in low molecular weight PAHs. [ABSTRACT FROM AUTHOR]

The coastal area between the mouths of the Aguas and Antas Rivers presents a deformed system of raised marine deposits, some of which have been strongly affected by active tectonics. The use of amino acid epimerization dating of Glycymeris shells from raised coastal deposits allowed determining the age of these marine deposits, all of them linked to highstand sea levels in the Mediterranean realm, with ages between MIS 11 and MIS 1. These results allowed corroborating the age of some previously studied sites, and using new sampling sites, the general aminostratigraphy for the Quaternary raised marine deposits on the Mediterranean coast was confirmed. The main deformation event took place after MIS 11 and continued until MIS 5, and was linked to the activity of the Palomares Fault. [ABSTRACT FROM AUTHOR]

We determined the lipid distributions ( n- alkanes, n- alkan-2-ones, n- alkanoic acids), total organic carbon (TOC), total nitrogen (TN), Ca/Mg and ash content in Las Conchas mire, a 3.2 m deep bryophyte-dominated mire in Northern Spain covering 8000 cal yr BP. Bog conditions developed in the bottom 20 cm of the profile, and good preservation of organic matter (OM) was inferred from n- alkanoic acid distribution, with the exception of the uppermost 20 cm (last ca. 200 yr). Microbial synthesis of long chain saturated fatty acids from primary OM likely produced a dominance of short chain n- alkanoic acids with a bimodal distribution, as well as the lack of correspondence between the n -alkane and n -alkanoic acid profiles in the upper 20 cm. This was accompanied by an increase in ash content, a decrease in TOC and variation in n- alkane ratios, thereby suggesting significant changes in the mire, namely drainage and transformation to a meadow, in the last ca. 200 yr. The distribution of n- alkan-2-ones indicated an increase in bacterial source from the bottom of the record to 94 cm, whereas their distribution in the upper part could be attributed mainly to plant input and/or the microbial oxidation of n- alkanes. The different n- alkane proxies showed variations, which we interpreted in terms of changes in vegetation (Sphagnum vs. non-Sphagnum dominated phases) during the last 8000 cal yr BP. C 23 was the most abundant homolog throughout most of the record, thereby suggesting dominant humid conditions alternating with short drier phases. However, such humid conditions were not linked to paleoclimatic variation but rather to geomorphological characteristics: Las Conchas mire, at the base of the Cuera Range, receives continuous runoff—even during drier periods—which is not necessarily accompanied by additional mineral input to peat, producing the development of Sphagnum moss typical of waterlogged ecotopes and damp habitats. Thus, although geochemical proxies indicated an ombrotrophic regime in the mire, geomorphological characteristics may make a considerable contribution to environmental conditions. [ABSTRACT FROM AUTHOR]

The lipid content of three cores from Lake Enol (Picos de Europa National Park, Asturias, Northern Spain) was studied. The n- alkane profiles indicated a major input from terrigenous plants [predominance of high molecular weight (HMW) alkanes] since ca. 1695 AD to the water body, although the uppermost cm revealed a predominance of organic matter (OM) derived from algae, as the most abundant alkane was C 17 . Three units revealing different environmental conditions were defined. Unit A (ca. 1695–1860 AD) in the lowermost parts of ENO13-10 (< 12 cm) and ENO13-15 (< 28 cm) was identified and was characterized by higher OM input and evidence of minimal degradation (high CPI values, predominance of HMW n- alkanoic acids and good correspondence between the predominant n- alkane and n- alkanoic acid chains). These findings could be linked to the Little Ice Age, when cold and humid conditions may have favored an increase in total organic carbon (TOC) and n -alkane and n -alkanoic acid content (greater terrigenous OM in-wash), and may have also reduced bacterial activity. In Unit B (ca. 1860–1980 AD) the lack of correspondence between the n -alkane and n -alkanoic acid profiles of ENO13-10 (12–4 cm) and ENO13-15 (28–8 cm) suggested a certain preferential microbial synthesis of long chain saturated fatty acids from primary OM and/or bacterial activity, coinciding with a decrease in OM input, which could be linked to the global warming that started in the second half of the 19th century. In ENO13-7 the low OM input (low TOC) was accompanied by some bacterial degradation (predominance of HMW n- alkanoic acids but with a bimodal distribution) in the lowermost 16–5 cm. Evidence of considerable phytoplankton productivity and microbial activity was especially significant in Unit C (ca. 1980–2013 AD) identified in the uppermost part of all three cores (5 cm in ENO13-7, 4 cm in ENO13-10 and 8 cm in ENO13-15), coinciding with higher concentrations of n- alkanes and n- alkanoic acids, which were considered to be linked to warmer and drier conditions, as well as to greater anthropogenic influence in modern times. Plant sterols, such as β-sitosterol, campesterol and stigmasterol, were significantly present in the cores. In addition, fecal stanols, such as 24-ethylcoprostanol from herbivores, were present, thereby indicating a continuous and significant pollution input derived from these animals since the 17th century, being more important in the last 20 years. [ABSTRACT FROM AUTHOR]

Abstract: Trace element concentrations in the Roñanzas peat bog record reveal a contribution of natural processes but the influence of anthropogenic factors predominates in the last two millenniums, particularly aerosol deposition linked to mining and industrial activities in northern Spain. We observed that the Roñanzas record can be considered a preserved environment, suitable to search for local (<50km), regional (50–150km) and/or long-distance human activity fingerprinting, specifically that related to the deposition of heavy metals such as Pb, Zn and Hg. We also carried out a multivariate statistical study in order to clarify the geochemical behavior of trace and major elements. Our study design represents a novel approach to assign natural vs. human contributions in peatlands. Therefore, synergies obtained by the simultaneous study of multivariate statistics and enrichment factors allow robust conclusions about paleoenvironmental evolution and human activities. Anthropogenic influence has also been reported in similar records in other parts of Europe, thereby suggesting large-scale sources for atmospheric pollution. However, here we revealed remarkable particularities, such as the association of Cd, Zn and Pb, mainly linked to regional and local factors (mining and more recently the metallurgical industry), whereas we propose that the occurrence of Hg is associated with a combination of regional factors and global atmospheric pollution. [Copyright &y& Elsevier]

Abstract: The sedimentary record of the volcanic lake known as the Fuentillejo maar (central Spain) offers the opportunity to determine the palaeoenvironmental evolution of the central-southern part of the Iberian Peninsula during the Middle and Upper Pleistocene. A total of 439 samples from the upper 88m of a ca. 142m long core (spanning the last ca. 355ka) were examined. The interval corresponds to the last 220ka of the record. High n-alkane CPI values and the presence of sulfur revealed that little diagenetic signal attenuation or modification had occurred. A number of n-alkane-based indices (e.g. predominant n-alkane, ACL, Paq and TARHC ratios, and the proportion of C27, C29 and C31 n-alkanes with respect to the summed C27 +C29 +C31) alkanes, showed changing conditions in the organic matter input to the maar lake over time, with episodes involving a major input of terrestrial vegetation, alternating with others in which algae or a mixed input of terrestrial plants, aquatic macrophytes and algae occurred. The proportions of C27, C29 and C31 were useful for reconstructing the palaeoenvironmental evolution of the basin as they allowed assignment of several dry intervals during which grasses developed, while during humid phases trees expanded at the expense of grasses. In general, we found good correspondence between these episodes and the climatic cycles observed in δ18O records from ices cores in Greenland and Antarctica, as well as from marine cores. Thus, we conclude that global palaeoclimatological changes were recorded in the maar record. Likewise, Heinrich Events appeared to be reflected in the n-alkane indices. This was confirmed by single spectral analysis and cross spectral analysis with the insolation curve on 21 July at a latitude of 65°N. The approach revealed that the cycles interpreted in the Fuentillejo record (103, 41, 23 and 19ka) showed evidence of orbital influence related to the astronomical cycles of the eccentricity variation in the Earth’s orbit, the Earth’s obliquity oscillation, and the precession variation (Milankovitch theory). [Copyright &y& Elsevier]

Dysfunctions of dopaminergic homeostasis leading to either low or high dopamine (DA) levels are causally linked to Parkinson's disease, schizophrenia, and addiction. Major sites of DA synthesis are the mesencephalic neurons originating in the substantia nigra and ventral tegmental area; these structures send major projections to the dorsal striatum (DSt) and nucleus accumbens (NAcc), respectively. DA finely tunes its own synthesis and release by activating DAD2 receptors (D2R). To date, this critical D2R-dependent function was thought to be solely due to activation of D2Rs on dopaminergic neurons (D2 autoreceptors); instead, using site-specific D2R knock-out mice, we uncover that D2 heteroreceptors located on non-DAergic medium spiny neurons participate in the control of DA levels. This D2 heteroreceptor-mediated mechanism is more efficient in the DSt than in NAcc, indicating that D2R signaling differentially regulates mesolimbic- versus nigrostriatal-mediated functions. This study reveals previously unappreciated control of DA signaling, shedding new light on region-specific regulation of DA-mediated effects. [ABSTRACT FROM AUTHOR]

Abstract: We determined the distribution of lipids (n-alkanes and n-alkan-2-ones) in present-day peat-forming plants in the Roñanzas Bog in northern Spain. Consistent with the observation of others, most Sphagnum (moss) species alkanes maximized at C23, whereas the other plants maximized at higher molecular weight (C27 to C31). We show for the first time that plants other than seagrass and Sphagnum moss contain n-alkan-2-ones. Almost all the species analysed showed an n-alkan-2-one distribution between C21 and C31 with an odd/even predominance, maximizing at C27 or C29, except ferns, which maximized at lower molecular weight (C21–C23). We also observed that microbial degradation can be a major contributor to the n-alkan-2-one distribution in sediments as opposed to a direct input of ketones from plants. [Copyright &y& Elsevier]

Abstract: The n-alkane components of sediments were measured in 530 samples taken from a 107m-long core in the Padul Basin (Andalusia, Spain) covering from the Lower Pleistocene (ca. 1Ma) to the mid-Holocene (ca. 4.5kaB.P.). We show that the relative percentages of the high molecular weight n-alkanes (C27, C29 and C31) are useful tools to reconstruct the ancient vegetation and palaeoclimatological evolution of this basin. On the basis of these proxies, we distinguished twelve long-term climatic periods linked to alternating dry/humid scenarios: 6 Dry Episodes alternating with 5 Humid Episodes were interpreted in the Pleistocene record, together with a final Episode covering the Holocene. Dry scenarios produced the recession of forests and the development of grasses, whereas the inverse pattern was interpreted during humid phases. The good correlation with the Guadix-Baza Basin record showed that, in most cases, dry periods coexisted with warm conditions, while humid ones were linked to temperate-colder conditions. Only during the last long-term Dry Episode of the Pleistocene, which coincided with the end of the Last Glacial Period, did low temperatures concur. The relative percentages of the high molecular weight n-alkanes also indicate rapid changes in vegetation produced by short-scale arid cycles during the last Glacial Period (<100kaB.P.), which are linked to the Heinrich Events and Younger Dryas. This interpretation has been confirmed by previous pollen analysis performed in the Padul Basin. Likewise, a correlation was observed with Marine Isotope Stages (MIS). These results show that vegetation responds to long-term cycles (orbital scale) and millennial-scale global cycles. Therefore, climatic variations in the Padul Basin responded to global climatic changes, although with local climatic effects. Good correspondence was also observed with elemental, isotopic and other molecular organic proxies, thereby amplifying the palaeoclimatological knowledge of the Padul Basin during the Pleistocene, especially in some spans that were previously unclear. [Copyright &y& Elsevier]

Of the five mammalian muscarinic acetylcholine (ACh) receptors, M5 is the only subtype expressed in midbrain dopaminergic neurons, where it functions to potentiate dopamine release. We have identified a direct physical interaction between M5 and the AP-3 adaptor complex regulator AGAP1. This interaction was specific with regard to muscarinic receptor (MR) and AGAP subtypes, and mediated the binding of AP-3 to M5. Interaction with AGAP1 and activity of AP-3 were required for the endocytic recycling of M5 in neurons, the lack of which resulted in the downregulation of cell surface receptor density after sustained receptor stimulation. The elimination of AP-3 or abrogation of AGAP1–M5 interaction in vivo decreased the magnitude of presynaptic M5-mediated dopamine release potentiation in the striatum. Our study argues for the presence of a previously unknown receptor-recycling pathway that may underlie mechanisms of G-protein-coupled receptor (GPCR) homeostasis. These results also suggest a novel therapeutic target for the treatment of dopaminergic dysfunction. [ABSTRACT FROM AUTHOR]

De Torres, T., Ortiz, J.E., Arribas, I., Delgado, A., Julià, R. & Martín-Rubí, J.A. 2009: Geochemistry of Persististrombus latus Gmelin from the Pleistocene Iberian Mediterranean realm. Lethaia, Vol. 43, pp. 149–163. In this paper the organic and inorganic geochemistry of fossil and extant Persististrombus latus are compared, together with other strombid species ( Lentigo lentiginosus, Lobatus gigas, Strombus alatus, Lobatus raninus, Laevistrombus canarium and Tricornis latissimus). Using a large sample of well-preserved fossil P. latus shells from the Mediterranean realm, we examined the warming period of sea water in the Middle Pleistocene. A mineralogical study of the shells demonstrates the continuous presence of calcite and a complex organic matter distribution, which was well preserved in many cases, thereby making the U/Th dating of strombid shells unreliable. U/Th analysis of coral samples and amino acid racemization dating of pelecypod shells confirmed that P. latus entered the Mediterranean realm in MIS 7 and 5. The oscillations of the δ18O values reflect annual growth periods and provide a mixing of the first signal record (primary growth) and successive overgrowths. □ Amino acid racemization, Mediterranean Sea, Persististrombus latus, shell mineralogy, U/ Th, δ 18 O. [ABSTRACT FROM AUTHOR]

Abstract: We determined the lipid distributions (n-alkanes, n-methyl ketones, n-alkanoic acids, 5-n-alkyl resorcinols and sterols) and total organic carbon (TOC) content in a 2.0m deep Sphagnum-dominated ombrotrophic peat bog in Northern Spain. From this, we inferred the changes in plant distribution (Sphagnum- vs. non-Sphagnum-dominated), which was related to palaeohydrological and palaeoenvironmental conditions, during the last 8000calyr BP. From n-alkane proxies, 10 dry/humid episodes were distinguished: five dry episodes alternating with five humid episodes, the transitions from dry to humid periods not necessarily being linked to changes in temperature. These transitions were found to correlate well with global environmental episodes and are consistent with other Spanish records. Our results suggest that the n-alkane carbon preference index (CPI) could be related to degradation rates linked to variation in temperature rather to changes in the amount of precipitation, whereas the 5-n-alkyl resorcinol/sterol ratio could reflect the abundance of sedges. [Copyright &y& Elsevier]

Abstract: Cave bears (Ursus deningeri and U. spelaeus) and hominids (Homo heidelbergensis, H. neanderthalensis, and H. sapiens) were potential competitors for environmental resources (subterranean and open air). Here, we examined the age at death of cave bear (Ursus spelaeus Rosenmüller-Heinroth) specimens from Amutxate cave in order to shed light on the effect of resource sharing between cave bears and hominids. After studying dental wear of the deciduous and permanent dentitions, the ontogenetic development of mandibles, and incremental layers of cement (annuli), we defined five age groups differentiated by marked development and size gaps. Our findings indicate that after hibernating, bears abandoned the den, thereby leaving the subterranean environment (caves) free for temporary hominid occupation—this would explain the subtle traces of hominid presence in many dens. However, a simple calculation based on age at death of subadult and adult cave bear specimens in Amutxate cave, extrapolated to the whole cave area, showed that the area surrounding this cave hosted bears for at least 9,000 years. This length of habitation, quite similar to the time-span derived from amino acid racemization and electron spin resonance, indicates that bear populations in the Amutxate cave constituted a serious constraint for hominid exploitation of the environment. [Copyright &y& Elsevier]

Abstract: A representative paleoenvironmental reconstruction of continental middle latitude from ca. 2my to the upper part of Middle Pleistocene (279±77ky) was obtained from the carbon and oxygen stable isotopes analyzed in ostracode shells (Cyprideis torosa) recovered in the Guadix-Baza Basin (SE Spain), an intramontaneous closed depression filled by alluvial and lacustrine sediments. This study was performed along a 356-m-thick composite section, dated previously by paleomagnetism and the amino acid racemization method. δ13C and δ18O profiles reflected changes in temperature, the evaporation/infill ratio in the water bodies and the amount of rain. δ13C is also affected by changes in plant biomass: periods with high δ13C and δ18O values are associated with warm and dry regimes, and with less vegetation, which, in some cases, coincide with the development of displacive gypsum crystals, whereas low δ13C and δ18O values correlate with cold and humid episodes, which cause more vegetation biomass and, therefore, increasing the input of isotopically light carbon. Intermediate δ18O values are linked to temperate dry or humid episodes when they coincide with high or low δ13C values, respectively. 86 paleoclimatic events were distinguished in the Pleistocene record from the δ13C and δ18O profiles. From both the statistical analysis of the geochemical data and the geological observations, four Cold and Humid Long Periods (low δ18O) and four Warm and Dry Long Periods (high δ18O) were defined. This differs with respect to the paleoclimatological behavior established for the Northern Hemisphere where during cold periods (glacial), no water was available while permafrost conditions persisted, whereas in warm episodes (interglacial), higher precipitation rates occurred. Good correspondences between the Guadix-Baza Basin paleoclimatic record and a marine oxygen-isotope sequence, two continental cores and other long Mediterranean paleoenvironmental records (pollen sequences from Israel) were found, which suggested that climate changes in the Guadix-Baza Basin were in tune with global climatic changes. [Copyright &y& Elsevier]

Age calculation algorithms for the D/L ratios of five amino acids (isoleucine, leucine, aspartic acid, phenylalanine and glutamic acid) analysed in continental ostracodes were determined for southern and central Iberian Peninsula, and allow the numerical dating of deposits in the Mediterranean area since Lower Pleistocene time to present. In order to obtain more accurate results for young samples, other algorithms were calculated for aspartic acid, phenylalanine and glutamic acid. Using these algorithms, together with paleomagnetism, the chronostratigraphy of the “composite-stratotype-section” of the east domain of the Guadix-Baza Basin that covers most of the Pleistocene (from the Plio/Pleistocene boundary to 279±77 ka) has been obtained. Ostracodes represent a formidable tool for amino acid racemization dating purposes in view of their abundance, valves mineralogy and the high degree of preservation of amino acids within their caparaces, even in old (Early Pleistocene) samples. These results suggest that the range of the amino acid racemization dating method in the Iberian Peninsula is older than 1.1 Ma. [Copyright &y& Elsevier]

• Based on alkane indices, three geochemical units (GU) were identified. • GUs represent major contribution of aquatic macrophytes or terrestrial plants. • Paleoenvironmental episodes (PE) produced oscillations in the marsh water level. • PEs were related to sea level and climatic changes, and recent tectonics. • Emersion led to increased amounts of short-chain and branched fatty acids. We reconstructed the paleoenvironmental conditions of the Mazarrón Basin during MIS 7 and MIS 1 based on their alkane and fatty acid contents, their mineralogy and the fossil content of an amino-acid-dated sediment sequence. The n- alkane and fatty acid indices proved to be excellent paleoenvironmental proxies for studying the paleo-hydrogeological and paleoclimatological evolution of this marshland. Three geochemical units (GUs) were identified from the abundance of the C 25 n -alkane and the ACL, TAR HC and P aq values, confirming the importance of phases with terrestrial plant input or aquatic macrophyte predominance. These GUs were used to define three paleoenvironmental episodes (PEs) during MIS 7. In PE7.1, the contribution of algal and aquatic macrophytes predominated in a temporarily flooded saline muddy plain. In PE7.2, the major contribution was from aquatic macrophytes (flooded marsh), although it was marked by episodes of emersion with greater terrestrial contribution. At the top of the MIS 7 record (PE7.3), there was a significant reduction in the water depth, with the main input deriving from terrestrial plants in a muddy alluvial plain. Six PEs were established during MIS 1 (Holocene), of which three predominately received organic matter derived from aquatic macrophytes, while the major contribution in the other three came from terrestrial plants. The two sets of PEs were linked to episodes of increased and decreased water level, respectively. This interpretation is consistent with the characteristics of the sediment facies, with PE1.1, 1.3 and 1.5 corresponding to a marsh with deeper water and a greater input of detrital materials, and PE1.2, 1.4 and 1.6 to a shallow environment with carbonates and gypsum deposits. Direct marine influence was limited, so the oscillations in the water level in the marsh were likely to be more related to climatic changes (drier/wetter phases) and recent tectonics than to large changes in sea level. Emersion led to degradation of the organic matter and enrichment in short-chain and branched saturated fatty acids. [ABSTRACT FROM AUTHOR]

A multiproxy study based on sedimentology, mineralogy, magnetic susceptibility, organic geochemistry and fossil content allowed to establish the sedimentary evolution of palustrine basins and to study the interplay between tectonic and climatic forcings in the sedimentation and facies arrangement that can be extrapolated to other coal-bearing basins. The reinterpretation of the data from 18 cores allowed to determine the facies distribution and to model the sedimentary evolution of the Padul Basin, with the longest continuous continental Quaternary record in the Southwestern Mediterranean region. The Padul Basin sediment record and facies successions provide an outstanding example of tectonically and environmentally controlled sedimentation. The sedimentary characteristics of the cores and thickness distribution revealed that recent tectonics was a more important forcing than other processes (e.g. climate). The influence of recent tectonics was determinant in facies arrangement, that is to say that the activity of a rotated fault produced a differential subsidence, causing more than 100 m of palustrine deposits to stack. On the basis of the sedimentological record combined with data on the mineralogy, fossil content, magnetic susceptibility and total organic carbon, three main sedimentary units were identified, linked to diverse subsidence rates and paleoenvironmental oscillations. The magnetic susceptibility was likely to have been controlled by the organic matter content (TOC values), linked to oxic/anoxic conditions. In the lower part of the record, Unit A (107.0–68.7 m), shallow lacustrine conditions were dominant, with an important influx associated with considerable runoff from active alluvial fans, linked to a higher subsidence rate. Unit B (68.7–37.6 m) had a transitional character, with a considerable decrease in the influence of the alluvial fan system. The lake recharge through overland flow markedly diminished and pre-existing groundwater recharge was dominant. A sudden change to peaty materials indicated that surface runoff was directly diverted to the recently excavated Dúrcal River gorge, thereby precluding the basin from becoming a swampy environment with stagnant waters. Unit C (upper 37.6 m) was almost exclusively fed by bicarbonate groundwater and subsurface runoff through the highly permeable coarse alluvial fan deposits. Within these main sedimentary units, minor mud-peat shallowing-upward sequences were identified. • The facies distribution and sedimentary evolution model along 1 Ma were determined • Recent tectonics was the dominant forcing and determinant in facies arrangement • The Garrido rotated Fault produced a differential subsidence at the NE corner • Sedimentary units showed distinct hydrogeological patterns linked to recent tectonics • Lacustrine conditions dominated at >400 ka; palustrine conditions occurred at <400 ka [ABSTRACT FROM AUTHOR]

The article reports the first example of the evolution of total enantioenrichment of the solid phase for an essential amino acid mediated by solution-phase racemization. According to the authors, the results show that the emergence of a state of solid-phase single chirality for a proteinogenic amino acid may be achieved in a near equilibrium process even in the absence of mechanical energy.

Summary Typical antipsychotics can cause disabling side effects. Specifically, antagonism of D2R signaling by the typical antipsychotic haloperidol induces parkinsonism in humans and catalepsy in rodents. Striatal dopamine D2 receptors (D2R) are major regulators of motor activity through their signaling on striatal projection neurons and interneurons. We show that D2R signaling on cholinergic interneurons contributes to an in vitro pause in firing of these otherwise tonically active neurons and to the striatal dopamine/acetylcholine balance. The selective ablation of D2R from cholinergic neurons allows discrimination between the motor-reducing and cataleptic effects of antipsychotics. The cataleptic effect of antipsychotics is triggered by blockade of D2R on cholinergic interneurons and the consequent increase of acetylcholine signaling on striatal projection neurons. These studies illuminate the critical role of D2R-mediated signaling in regulating the activity of striatal cholinergic interneurons and the mechanisms of typical antipsychotic side effects. [ABSTRACT FROM AUTHOR]

In this paper, we conduct a palynological analysis of a high-resolution Holocene record from Cartagena Bay, southeast of the Iberian Peninsula, to establish paleoenvironmental variability of coastal areas in the western Mediterranean region at a centennial-scale over the last 7300 years. Statistical analysis of four palynozones allows reconstruction of paleotemperature and paleohumidity conditions. Pinus , steppic, xerophilous, and Mediterranean taxa persisted continuously through the record, and only during periods of increased humidity did deciduous and Mediterranean taxa expand (Zones II, subzone IIIb). Cooler and dry conditions favored the development of Cupressaceae and scrubs between 7300 and 7000 yr cal BP. The mid-Holocene (Northgrippian) mesophytic optimum took place between 6800 and 4000 yr cal BP during which time a Mediterranean climate was present and open forest developed, predominantly consisting of Mediterranean taxa and deciduous trees. The gradual rise in aridity in the Meghalayan (4000–1700 yr cal BP) led to Mediterranean forest being replaced by steppic and xerophilous vegetation, a change related mostly to a decrease in summer insolation, with superimposed centennial-scale variability in humidity. In parallel with forest degradation caused by increasing aridity, the record shows marked evidence of human influence since 4000 yr cal BP, which accelerated the progression of open landscapes from the Chalcolithic onwards, this change being especially marked during the Roman period. Significant denudation of the landscape can be attributed to the use of fire, as well as due to agriculture and grazing, with a major contributor being intense metallurgical and mining activity in the area. The Cartagena Bay record reported herein shows centennial-scale oscillations in humidity and temperature that correlate with well-known climatic events during the late Holocene in the western Mediterranean region, synchronous with variability in solar and atmospheric dynamics. The alternation of persistent North Atlantic Oscillation modes is likely to have played a key role in regulating humid–arid periods. • Pollen content allowed the paleoenvironmental reconstruction during the Holocene. • Centennial-scale oscillations in humidity & temperature correlate with climatic events. • The mid-Holocene mesophytic optimum took place between 6800 and 4000 yr cal BP. • Aridity and xerophytization occurred between 4000 and 1700 yr cal BP. • Human influence accelerated the progression of open landscapes since the Chalcolithic. [ABSTRACT FROM AUTHOR]

Background: Metachromatic Leukodystrophy (MLD, OMIM 250100) is a neurodegenerative disease caused by mutations in the ARSA gene (OMIM 607574) that lead to deficiency in Arylsulfatase A (ASA). ASA pseudodeficiency (PD‐ASA) is a biochemical condition that substantially diminishes ASA activity but is not associated with clinical manifestations. PD‐ASA is associated with the c.1055A>G (p.Asn352Ser) (rs2071421) and c.*96A>G (rs6151429) variants, which have an estimated frequency of 2% in the population. Objective: To determine the activity of Arylsulfatase A and to identify variants and haplotypes in the ARSA gene in Mexican individuals with pseudodeficiency. Methods: Two‐hundred apparently healthy individuals were included to determine the enzymatic activity of ASA in leukocytes by spectrophotometric analysis, and identification of the PD‐ASA alleles was performed by PCR‐RFLP assays. Genotypes were confirmed by semi‐automated Sanger sequencing. Haplotypes were constructed using Arlequin v.10.04, and linkage disequilibrium analysis was performed with Cube X. Results: The enzymatic activity of ASA was determined to be 1.74–2.09 nmol/mg protein/min and later correlated with genotypes and haplotypes. For the (p.Asn352Ser) variant, we found 126 (0.63) individuals with the AA genotype, 62 with AG (0.31) and 12 with GG (0.06); the frequency of the polymorphic allele was 0.215 (86 alleles, 21.5%), and the variant was in HWE (p =.2484). The variant c.*96A>G was also in HWE (p =.2105): 185 individuals (0.925) with the AA genotype, 14 (0.07) with AG, and 1 (0.005) with (GG), with a frequency of 0.04 (4%) for the polymorphic allele. The inference of haplotypes resulted in 312 (0.78) AA, 72 (0.18) GA, and 16 (0.04) GG haplotypes. The AG haplotype was not found. The variants were found to be in linkage disequilibrium (D' = 1). Of the nine possible diplotypes, AA/AG, AA/GG, and AG/GG were not found, in concordance with the hypothesis that the G allele of c.*96A>G does not occur in the absence of the G allele of c.1055A>G. We found a slight correlation between ASA biochemical activity and variants, mainly due to the G allele of c.*96A>G in either genotypes or haplotypes. Conclusions: In Northwestern Mexico, the presence of PD‐ASA alleles was biochemically and molecularly determined, and the frequencies were found to be in HWE. The frequency of PD‐ASA for the North Western Mexican mestizo is 8%. [ABSTRACT FROM AUTHOR]

A straightforward unprecedented sublimation protocol that reveals both conversion of a racemic compound into a racemic conglomerate and subsequent enantioenrichment has been developed for the proteinogenic amino acid valine. The phenomenon has been observed in closed and open systems, providing insight into asymmetric amplification mechanisms under presumably prebiotic conditions. [ABSTRACT FROM AUTHOR]

Conglomerate crystallization is required for many deracemization or enantioenrichment protocols. Here, we report the metal-mediated mechanochemical transformation of racemic compounds of some proteinogenic amino acids – valine, leucine and isoleucine – into their corresponding conglomerates. Specifically, ZnO has the ability to promote and stabilize the conglomerate phase of these amino acids to an extent where the racemic compound is not observed. [ABSTRACT FROM AUTHOR]

This paper presents a detailed geological and geomorphological analysis of the so‐called givoni (low‐relief, mainly gravelly landforms subparallel to the coastline) associated with the MIS 5 terrace in the northern Gulf of Taranto (southern Italy). These landforms can be interpreted as former beach ridges, swash/drift‐aligned spits, or swash/drift‐aligned barriers (BSBs); thus, givoni are palaeoshoreline indicators. In the study area, recognizing the classic landforms associated with marine terraces, that is, surfaces and scarps, is difficult, as the givoni are often associated and variably combined with surfaces and scarps. Thus, we reconstruct the formation and evolution processes of the MIS 5 marine terrace, including the formation of surfaces, scarps, and BSBs (and the resulting composite landforms), in an overall evolutionary framework based on eustatic oscillations. Then, we reconstruct a complete set of situations in which BSBs form on loose or semiconsolidated substrates in response to eustatic oscillations: (a) BSBs can form during a highstand of a warm stage on previously consolidated sediment; (b) BSBs may represent coastlines formed during sea‐level standstills in the context of a general regressive phase following the highstand peak that created a relict sea cliff; (c) BSBs may represent coastlines formed during a new relative highstand in a warm substage on previously unconsolidated deposits formed during the same stage; and (d) BSBs may be formed by a process similar to that of the previous case, except that the sea level stopped rising against a pre‐existing BSB. [ABSTRACT FROM AUTHOR]

The predominantly carbonate nature of the mountains near the coast of Málaga and Marbella (Costa del Sol, southern Spain) and the presence of springs have favored the formation of travertine buildups during the Quaternary. The geomorphic characteristics of the slopes and the location of the springs have determined the development of three types of travertine growths: (1) spring travertines, located preferentially on the south mountainside, where the slope is steepest; (2) pool-dam-cascade travertines, which form along the north and east edges, far from the carbonate relief and with a gentler slope; and (3) river-valley travertines, formed in the courses of the springs of any sector. Field observations combined with new amino acid racemization (AAR) dating of Helicidae gastropods show that most of the travertine formations are polyphasic and that their development was interrupted by stages of erosion and incision. Five stages of travertine development are evident, most of which are related to warm, moist episodes corresponding to marine oxygen isotope stages (MIS) 7, 5, 3, and 1, although local travertine growth also occurred during MIS 6 and during the transition from MIS 3 to 2. [ABSTRACT FROM AUTHOR]

Abstract: Amphetamine-type stimulants (ATS) are the second most consumed illicit drug worldwide and lack good treatments for associated substance use disorders, lagging behind other addictive drugs. For this reason, a deeper understanding of the pharmacodynamics of ATS is required. The present study seeks to determine amphetamine (AMPH) enantiomers' effects on the homomeric α7 nicotinic acetylcholine receptor (α7 nAChR). Here we have shown that AMPH enantiomers bind to the α7 nAChR and competitively inhibit acetylcholine responses. Our in silico docking analysis suggests that AMPH binds close to the β7 strand of the B-loop of a chimera comprising of the human α7 nAChR and the acetylcholine binding protein from Lymnaea stagnalis. This may inhibit the required movement of the C-loop for channel opening, due to steric hindrance, providing a structural mechanism for its antagonist effect. Finally, we have shown that, in α7 nAChR full knockout mice, the behavioral response to D-AMPH is attenuated, providing direct evidence for the role of α7 nAChRs on the physiological response to D-AMPH. Importantly, D-AMPH exerts these effects at concentrations predicted to be pharmacologically relevant for chronic methamphetamine users and during binges. In conclusion, our data present new findings that implicate the α7 nAChR on the pharmacodynamics of ATS, which may be important for behavioral responses to these drugs, indicating a potential role for α7 nAChRs in ATS substance-use disorders. Highlights • Amphetamine competitively inhibits α7 nicotinic receptors at physiological levels. • Amphetamine binding site localization is directed by hydrogen bonding to Ser144. • α7 receptor full knock-out mice display altered behavioral response to amphetamine. • The α7 receptor could be a potential target for treatment of AMPH abuse. [ABSTRACT FROM AUTHOR]

Here, we sought to reconstruct the Pleistocene and Holocene evolution of Cartagena Bay. Therefore, 16 borehole cores were analysed with the following aims: (1) to define a chronological framework; (2) to obtain data on the palaeoenvironment; and (3) to establish the relationship with human activities, especially focused on the reconstruction of the Carthago Nova (also known as Qart Hadasht) conquest. A total of 147 samples were recovered for amino acid racemisation (AAR) dating; 32 for radiocarbon dating (14C); and 159 for sedimentological, palaeontological, and biomarker determination. These approaches allowed us to elucidate the evolutionary phases of the palaeolandscape in Cartagena. The simultaneous use of AAR and 14C dating allowed the discrimination of spurious ages and the establishment of a chronological scale. During the Marine Isotope Stages (MIS) 7 and 5, the sea level (SL) in Cartagena Bay was almost the same as today. An alluvial plain developed in the northern area, and a delta was formed by an ephemeral river. In contrast, during MIS4, after a fall in SL, a wide sandy coastal plain emerged, leading to the accumulation of colluvial and aeolian deposits. The Holocene transgression was reflected in the hinterland in a late and temporarily floodable marsh fed by alluvial fans and creeks, producing a salinity gradient from freshwater to brackish and saline waters. Along the sea front, the marine influence was evident but not dominant, grading up and landwards to saline and freshwater marshes. Therefore, at the time of Scipio's conquest, the geography of Carthago Nova was quite different from that described by Polybius. The Roman's sudden attack seized Qart Hadasht from the south-west, avoiding the marshy area and not crossing a fast and deep ebb stream as it never existed on the Mediterranean Iberian coast. [ABSTRACT FROM AUTHOR]

We describe a patient severely affected with multiple congenital anomalies, including brain malformations and skeletal dysplasia suggestive of cranioectodermal dysplasia (CED) ciliopathy, who unusually carries several homozygosity tracts involving homozygous missense mutations in SPAG17 (exon 8; c.1069G > C; p.Asp357His) and WDR35 (exon 13; c.1415G > A; p.Arg472Gln) as revealed by homozygosity mapping and next generation sequencing. SPAG17 is essential for the function and structure of motile cilia, while WDR35 belongs to the same intraflagellar transport (IFT) gene family whose protein products are part of functional IFT A and B complexes. Formerly, SPAG17 was related – through polymorphic variants – to an influence on individuals’ height; more recently, Spag17 −/− mice models were reported to present skeletal and bone defects, reduced mucociliary clearance, respiratory distress, and cerebral ventricular enlargement. Homozygous or compound heterozygous mutations in WDR35 have mainly been related to CED2 or short-rib thoracic dysplasia 7, with only three cases showing some brain anomalies. Given that our patient presents these clinical features and the close functional relationship between SPAG17 and WDR35 , it is feasible that the combined effects from both mutations contribute to his phenotype. To our knowledge, this patient is the first to harbor a likely pathogenic homozygous mutation in both genes at the same time. Thus, the resulting complex phenotype of this patient illustrates the heterogeneity associated with ciliopathies and further expands the clinical and mutational spectrum of these diseases. Finally, we highlight the combined use of high-throughput tools to diagnose and support the proper handling of this and other patients. [ABSTRACT FROM AUTHOR]

In the Almenara marsh (western Mediterranean), four cores were analyzed to establish the relationship between the marsh record of the Almenara marshlands and the environmental factors responsible for its evolution during the Holocene. One hundred and eighty-six samples were collected for sedimentologic and paleontological study: 63 for biomarker analysis; 5 for amino acid racemization (AAR) dating; and 5 for 14C dating. Litho and biofacies analyses identified distinct paleoenvironments, with the presence of a marsh environment alternating with inputs of alluvial material and marine sediments. Biomarkers indicated the constant presence of terrestrial (herbaceous) plants, together with a variable development of aquatic macrophytes. During the Holocene transgression, the Almenara marsh was occupied by oligohaline marsh facies with an oscillating water level and peat formation, which was established at the bottom of the record at 7570 cal yr BP and persisted until 3100±780 yr (AAR). Maximum surface flooding occurred at 5480 cal yr BP, registered 450m from the current coastline. At least three peat beds (dated with 14C dating and AAR) correlated with Bond (episode 5900 cal yr BP) and Wanner (episodes 4800–4500 and 3300–3500 cal yr BP) cycles and thus correspond to a regional model that affected the Northern Hemisphere. [ABSTRACT FROM PUBLISHER]

To refine knowledge about terrace phases and uplift history for a tectonically poor deformed region, we apply the synchronous correlation method to reconstruct the chronology of a poorly constrained sequence of raised palaeoshorelines on the Apulian foreland, southern Italy. This work uses new chronological constraints obtained by amino acid racemisation (AAR) and isoleucine/alloisoleucine epimerisation (IE) on Patella spp., Thetystrombus latus (Gmelin), Glycymeris sp., and ostracods and U-series dating on corals Hoplangia durotrix Gosse and Cladocora caespitosa Linneo. This procedure provides a quantitative estimate of the vertical movements and associated rates within a region of the Apulian foreland. The synchronous correlation method uses sea-level highstands and uplift rate(s) as inputs; in particular, for sea-level highstands, the inputs are the age of the highstands and the sea-level elevation of the highstands relative to the present-day sea level. The output is a set of currently expected elevations of each sea-level highstand (the present elevations of palaeoshorelines). We then used regression analysis to assess the robustness between our observed palaeoshorelines and expected elevations of sea-level highstands. Our results show that the best fitting scenario is obtained using the sea-level curves of (i) Waelbroeck et al. (2002) from present to 410 ky BP and (ii) Rohling et al. (2014) from 410 to 590 ky BP as inputs for our synchronous correlation method, with uplift rates ranging from 0.09 mm/y to 0.07 mm/y with a mean value of 0.08 mm/y from 590 ky BP onwards. We recognised palaeoshorelines in the field belonging to the following highstands: 120 ky BP (MIS 5.5, second peak), 127 ky BP (MIS 5.5, first peak), 212 ky BP (MIS 7.3), 330 ky BP (MIS 9.3), 410 (MIS 11), 525 ky BP (MIS 13.3), and 590 ky BP (MIS 15). Our results show field observations of the reoccupation effect of younger palaeoshorelines over older ones due to the relatively slow uplift rates measured in the investigated area as predicted by our synchronous correlation method. In particular, we show a well-mapped and described reoccupation of the MIS 5.5 palaeoshoreline over the MIS 7.3 palaeoshoreline, constrained by new absolute dating. In addition, the data from the Apulian foreland suggest an MIS 7.3 highstand close to the present sea level. • We apply the synchronous correlation method in order to reconstruct palaeoshorelines. • Three palaeoshorelines dating back to two highstand of MIS 5.5 • Re-occupation of older palaeoshorelines by younger due to low uplift rates • Sea level for the MIS 7.3 highstand close to the present sea level [ABSTRACT FROM AUTHOR]

In this work, we reconstruct a change in the wind regime and sea level pressure pattern during marine isotope stage (MIS) 5.5. To obtain these results, we studied two elements of the landscape south of the city of Gallipoli (Apulia region, southern Italy), namely, the Carmine-Li Foggi palaeo-littoral ridge (CLlr) and a field of domal-longitudinal fossil dunes present in the Il Campo locality, both dating back to MIS 5.5, through the use of geological and geomorphological surveys together with geochronological analyses by Uranium series and amino acid racemization/epimerization. A detailed study was carried out on the aeolian units within CLlr (AU1 and AU2) and the fossil dunes of the Il Campo locality (AU3) to reconstruct the palaeo-directions of the winds and, possibly, the sea level pressure patterns. AU1 was the first aeolian unit to settle. The accumulation of AU1 at the northern and southern edges of CLlr and its internal structure indicate effective aeolian transport both towards the N and S. Based on the principle of actualism,the AU1 unit allows us to recognise a "first aeolian phase" characterised by the alternation of winds from the S and NW. It involves an autumn–winter pressure pattern characterised by an Atlantic footprint similar to the current pattern: the Atlantic depressions entering the Mediterranean caused, as occurs today over Apulia, the alternation of winds from the S and NW before and after the passage of the low-pressure minima, respectively. In spring–summer, the pressure fields were likely very similar to the current pressure fields, with the Azores high dominating the central–western Mediterranean and the low pressure dominating the eastern Mediterranean, with winds not able to significantly impact sand transport, just as occurs today; this summer regime left the prevailing imprint of the Atlantic winter regime and therefore NW–S bimodality. AU2 and AU3 settled later than AU1 in a "second aeolian phase" of MIS 5.5. AU2 is characterised by south-eastward-dipping foresets. AU3 consists of domal and linear dunes oriented in the NW–SE direction. We interpret AU2 and AU3 as coastal dunes originating in a prevailing NW wind regime. Based on the principle of actualism and on literature data, we conclude that AU2 and AU3 settled under a pressure pattern which in fall–winter was similar to the current pattern, that is, characterised by Atlantic cyclones transiting over the Mediterranean, and the consequent NW–S bimodality of the winds. In the spring–summer, instead, the pattern was characterised by a pressure gradient from west (high) to east (low) higher than the current pressure gradient; this gradient caused stronger NW winds compared to today over the Apulia, according to a similar (but increased) mechanism which today, on the Aegean Sea, causes the development of the Etesio-Meltemi summer winds. Such strong summer winds from the NW, which were effective for sand transport, coupled with the NW–S bimodality in fall–winter, caused the overall prevalence of NW winds during the "second aeolian phase". This summer pressure gradient over the Mediterranean from west (high) to east (low) greater than today was caused by a summer strengthening of the east Mediterranean low-pressure branch, in turn caused by the northward shift of the intertropical convergence zone (ITCZ), which was widely documented during the sapropel S5 event and verified during MIS 5.5 after sea level had risen to the highstand. • Geological and geomorphological study of coastal MIS 5.5 deposits of Apulia (Italy). • Change in the wind regime and pressure pattern during MIS 5.5. • First "aeolian phase" of MIS 5.5 characterised by the alternation of winds from the S and NW. • Second "aeolian phase" of MIS 5.5 characterised by NW prevailing winds. • Summer pressure gradient over the Mediterranean from west to east greater than today. • Summer pressure gradient greater than today due to northward shift of ITCZ. [ABSTRACT FROM AUTHOR]

Here we present a pluridisciplinary study of Cuesta de la Bajada site (Teruel, Spain). Our findings show that the site contains an early Middle Paleolithic assemblage similar to other European early Middle Paleolithic industries, allowing us to evaluate the coexistence of this industrial tradition with the Acheulean technocomplex in southwest Europe. The process of lithic production at Cuesta de la Bajada represents a technology focused on debitage, the application of technical concepts such as ramified production sequences, and the recycling of flakes via the resharpening of tools and exhausted cores. This site was formed around a pond not far from a river and contains remains of large macrofauna other than equids and cervids. Taphonomic analysis highlights the abundance of cut marks on bones, and supports the hypothesis of selective hunting by hominids. The numerical ages derived from the combination of ESR, OSL and AAR dating methods indicate that the archaeological site was very likely formed around the MIS 8-MIS 9. The appearance of Middle Paleolithic industries in Europe could represents the autochthonous development of a technocomplex distinctly different from the Acheulean, characterised by chaînes opératoires of debitage and a progressive increase of Levallois technology and retouched tools. These results suggest that there is a clear coexistence of assemblages with Acheulean and Middle Paleolithic industries during the last third of the Middle Pleistocene at least in the Iberian Peninsula. [ABSTRACT FROM AUTHOR]

We studied two middle Pleistocene terraced deposits exposed along the Trani cliff and at Coppa Nevigata in the Apulia region, southern Italy. In particular, our study focused on stromatolitic units that are present at two sites. At the Trani cliff, Unit I consists of cemented, whitish, fine-grained, massive or bedded limestone. The limestone grades upwards into massive, porous bioconstructed calcareous bodies composed of in situ Charophyta stems and/or stromatolites. The uppermost part of the unit is composed of whitish calcarenite/calcisiltite layers with Characeae. The interpreted sedimentary environment for this unit is a hypersaline-brackish lagoon. At Coppa Nevigata, the NVI unit is composed of tawny or yellow ochre sand with rare polygenic centimetric pebbles. The sand grades upwards into light yellow and ochre sandy/clayey silt or clay. Some layers are cemented and form marly limestones which contains columnar stromatolites. The uppermost part of the unit consists of yellow ochre or tawny marly limestones and marls that are rich in external moulds of Abra sp. and Cerastoderma glaucum. The interpreted sedimentary environment for this unit is a brackish lagoon. Unit I and the NVI unit have been dated to MIS 9 and MIS 11, respectively, by applying the Amino Acid Racemisation (AAR) method to ostracod shells. The stromatolites of the NVI unit are ascribable to SH type, whereas those of Unit I are ascribable to SH and LLH types and to colloform type. In particular, the stromatolites at the Trani cliff are similar in shape and sedimentary environment to the modern stromatolites in Shark Bay (Australia). The water temperature and salinity conditions under which the current stromatolites live indicate that tropical/subtropical conditions were present in the Mediterranean Sea during MIS 11 and MIS 9. Our reconstructions suggest that: 1) during MIS 11, the sea surface temperatures (SSTs) were consistent with literature data, that indicate SSTs ∼3 C° higher than the current ones. 2) during MIS 9, the lagoon in which Unit I formed had a mean water temperature of the coldest month at least 10–12 C° higher than that in modern southern Adriatic and at least 3–4 C° higher than that in some modern north-African lagoons. Therefore, our study supports the hypothesis that the Mediterranean Sea experienced tropical/subtropical conditions during MIS 9 that were similar to those of MIS 11. [ABSTRACT FROM AUTHOR]

NMDA receptor activity is involved in shaping synaptic connections throughout development and adulthood. We recently reported that brief activation of NMDA receptors on cultured ventral midbrain dopamine neurons enhanced their axon growth rate and induced axonal branching. To test whether this mechanism was relevant to axon regrowth in adult animals, we examined the reinnervation of dorsal striatum following nigral dopamine neuron loss induced by unilateral intrastriatal injections of the toxin 6-hydroxydopamine. We used a pharmacological approach to enhance NMDA receptor-dependent signaling by treatment with an inhibitor of glycine transporter-1 that elevates levels of extracellular glycine, a coagonist required for NMDA receptor activation. All mice displayed sprouting of dopaminergic axons from spared fibers in the ventral striatum to the denervated dorsal striatum at 7 weeks post-lesion, but the reinnervation in mice treated for 4 weeks with glycine uptake inhibitor was approximately twice as dense as in untreated mice. The treated mice also displayed higher levels of striatal dopamine and a complete recovery from lateralization in a test of sensorimotor behavior. We confirmed that the actions of glycine uptake inhibition on reinnervation and behavioral recovery required NMDA receptors in dopamine neurons using targeted deletion of the NR1 NMDA receptor subunit in dopamine neurons. Glycine transport inhibitors promote functionally relevant sprouting of surviving dopamine axons and could provide clinical treatment for disorders such as Parkinson's disease. [ABSTRACT FROM AUTHOR]

Brain metastases are a significant cause of morbidity and mortality for patients with cancer, yet preventative and therapeutic options remain an unmet need. The cytokine sigment epithelium--derived factor (PEDF) is downregulated in resected human brain metastases of breast cancer compared with primary breast tumors, suggesting that restoring its expression might limit metastatic spread. Here, we show that outgrowth of large experimental brain metastases from human 231-BR or murine 4T1-BR breast cancer cells was suppressed by PEDF expression, as supported by in vitro analyses as well as direct intracranial implantation. Notably, the suppressive effects of PEDF were not only rapid but independent of the effects of this factor on angiogenesis. Paralleling its cytotoxic effects on breast cancer cells, PEDF also exerted a prosurvival effect on neurons that shielded the brain from tumor-induced damage, as indicated by a relative 3.5-fold reduction in the number of dying neurons adjacent to tumors expressing PEDF. Our findings establish PEDF as both ametastatic suppressor and a neuroprotectant in the brain, highlighting its role as a double agent in limiting brain metastasis and its local consequences. Cancer Res; 72(1); 144--53. ©2012 AACR. [ABSTRACT FROM AUTHOR]

Dopamine D2 receptor antagonism is a unifying property of all antipsychotic drugs in use for schizophrenia. While often effective at ameliorating psychosis, these drugs are largely ineffective at treating negative and cognitive symptoms. Increasing attention is being focused on the complex genetics of the illness and the signaling pathways implicated in its pathophysiology. We review targeted approaches for pharmacotherapy involving the glutamatergic, GABAergic and cholinergic pathways. We also describe several of the major genetic findings that identify signaling pathways representing potential targets for novel pharmacological intervention. These include genes in the 22q11 locus, DISC1, Neuregulin 1/ErbB4, and components of the Akt/GSK-3 pathway. [Copyright &y& Elsevier]

Abstract: The geologic study of the Apulian Tavoliere plain (Apulia region, southern Italy) is extremely difficult due to the scarcity of outcrops and fauna that could be used for dating. The survey in progress of the 1:50,000 scale geological sheet no. 409 “Zapponeta” (including the coastal zone of the Apulian Tavoliere) has prompted us to tackle this problem by using a large set of borehole data and the AAR dating method applied to ostracod shells, which are capable of colonizing all types of environment as long as there is water. This alternative approach has allowed us to recognise nine stratigraphic units or synthems and, for the first time in this area, to date them, and to find a correlation between them and the cycles of sea level variation. The recognised stratigraphic units are: the Coppa Nevigata sands (NEA; middle Pleistocene: MIS 17–16), argille subappennine unit (ASP; middle Pleistocene: MIS 15–13), the Coppa Nevigata synthem (NVI; middle Pleistocene: MIS 11), the Amendola subsynthem (MLM1; middle Pleistocene: MIS 11), an undifferentiated continental unit (UCI; middle Pleistocene: MIS 8–7), the Foggia synthem (TGF; middle–late Pleistocene: MIS 6), the Carapelle and Cervaro streams synthem (RPL; late Pleistocene: MIS 5–3), and the Inacquata farm synthem (NAQ; Holocene). Within the RPL unit, a buried Cladocora caespitosa bioherm referable to MIS 5.5, lacking in warm fauna, and in which the coral is embedded in clay has been found in some boreholes. This is the first finding of Tyrrhenian deposits with C. caespitosa along the Italian Adriatic coast; the presence of this coral in clayey sediments, a very uncommon occurrence, strengthens the hypothesis that the major fossil reefs grew in coastal waters that were characterised by alluvial inputs of fine sediments, higher turbidity, and higher temperature than today. In addition, on the basis of the current evidence, some consideration about the fauna of the MIS 5.5 layer allows us to hypothesise that the Adriatic Sea underwent a more moderate warming compared to that of the Ionian and Tyrrhenian seas. Instead, the finding in the NVI unit of a tropical lagoonal deposit with stromatolites referred to MIS 11 proves that the warming in this stage was undoubtedly greater than that of MIS 5.5. The MM4 borehole, which goes through the MIS 5 layers of the RPL unit, made it possible to recognise two marine phases during MIS 5: the first is referable to the MIS 5.5–5.3 interval, and the second to MIS 5.1. MIS 5.2 is marked by land emersion, whereas no evidence of land emersion between MIS 5.5 and 5.3 has been found. Also for the first time in this area, uplifting and subsiding areas have been recognised and the vertical movements assessed. In general, the data suggest that the Garganic Apulian foreland and the Amendola highland experienced an uplift, while the central-southern part of the study area, belonging to the Apulian Tavoliere plain, suffered a subsidence with rates increasing from north–northwest to south–southeast. In particular, the finding of the MIS 5.5 buried layer with C. caespitosa has allowed us to fill a gap in the data regarding the recent tectonic movements along the Adriatic coast (). This feature proves that there has been a recent subsidence event since MIS 5.5 in the coastal area of the Apulian Tavoliere plain. [Copyright &y& Elsevier]

The Tajo Basin is one of the richest in Mg-clays known around the world. Mg-bentonites, kwon as pink clays and green clays, alter in the Intermediate Unit of the Miocene sediments. In this work, a new approach to the genesis of these bentonites is performed by studying for the first time the biomarkers present in these clays in relation to the mineralogy and geochemistry, as well as using discriminatory criteria between green and pink clays. Samples were collected at a quarry of Mg-bentonites, in the proximities of Esquivias (Toledo, Spain). Mineralogical characterization and semi-quantification (X-ray diffraction (XRD)) allowed a well-defined classification according to the mineralogical content of the samples to be established, differentiating four associations. Geochemical analyses are clearly linked to the mineralogy and provide criteria to differentiate the genesis of the materials studied. In this regard, green clays are interpreted as having a more detrital character than pink clays, which present a more authigenic character. Biomarkers (n-alkanes and n-alkanoic acids) were studied, not showing a clear link with the mineralogy as in the case of the geochemistry, but providing interesting information about the origin and degradation of the organic matter. Pink clays have higher contents in biomarkers than green clays, providing a discriminative criterion. [ABSTRACT FROM AUTHOR]