Spatial and temporal patterns of pore water chemistry in the inter-tidal zone of a high energy beach

Submarine groundwater discharge (SGD) is a ubiquitous source of meteoric fresh groundwater and recirculating seawater to the coastal ocean. Due to the hidden distribution of SGD, as well as the hydraulic- and stratigraphy-driven spatial and temporal heterogeneities, one of the biggest challenges to date is the correct assessment of SGD-driven constituent fluxes. Here, we present results from a 3-dimensional seasonal sampling campaign of a shallow subterranean estuary in a high-energy, meso-tidal beach, Spiekeroog Island, Northern Germany. We determined beach topography and analyzed physico-chemical and biogeochemical parameters such as salinity, temperature, dissolved oxygen, Fe(II) and dissolved organic matter fluorescence (FDOM). Overall, the highest gradients in pore water chemistry were found in the cross-shore direction. In particular, a strong physico-chemical differentiation between the tidal high water and low water line was found and reflected relatively stable in- and exfiltrating conditions in these areas. Contrastingly, in between, the pore water compositions in the existing foreshore ridge and runnel system were very heterogeneous on a spatial and temporal scale. The reasons for this observation may be the strong morphological changes that occur throughout the entire year, which affect the exact locations and heights of the ridge and runnel structures and associated flow paths. Further, seasonal changes in temperature and inland hydraulic head, and the associated effect on microbial mediated redox reactions likely overprint these patterns. In the long-shore direction the pore water chemistry varied less than the along the cross-shore direction. Variation in long-shore direction was probably occurring due to topography changes of the ridge-runnel structure and a physical heterogeneity of the sediment, which produced non-uniform groundwater flow conditions. We conclude that on meso-tidal high energy beaches, the rapidly changing beach morphology produces zones with different approximations to steady-state conditions. Therefore, we suggest that zone-specific endmember sampling is the optimal strategy to reduce uncertainties of SGD-driven constituent fluxes

Lysergic acid diethylamide (LSD) and Psilocybin for the Management of Patients with Persistent Pain: A Potential Role?

Recently, there has been interest in lysergic acid diethylamide (LSD) and psilocybin for depression, anxiety and fear of death in terminal illness. The aim of this review is to discuss the potential use of LSD and psilocybin for patients with persistent pain. LSD and psilocybin are 5-hydroxytryptamine receptor agonists and may interact with nociceptive and antinociceptive processing. Tentative evidence from a systematic review suggests that LSD (7 studies, 323 participants) and psilocybin (3 studies, 92 participants) may be beneficial for depression and anxiety associated with distress in life-threatening diseases. LSD and psilocybin are generally safe if administered by a healthcare professional, although further investigations are needed to assess their utility for patients with persistent pain, especially associated with terminal illnes

Functionally Relevant Domains of the Prion Protein Identified In Vivo

The prion consists essentially of PrPSc, a misfolded and aggregated conformer of the cellular protein PrPC. Whereas PrPC deficient mice are clinically healthy, expression of PrPC variants lacking its central domain (PrPΔCD), or of the PrP-related protein Dpl, induces lethal neurodegenerative syndromes which are repressed by full-length PrP. Here we tested the structural basis of these syndromes by grafting the amino terminus of PrPC (residues 1–134), or its central domain (residues 90–134), onto Dpl. Further, we constructed a soluble variant of the neurotoxic PrPΔCD mutant that lacks its glycosyl phosphatidyl inositol (GPI) membrane anchor. Each of these modifications abrogated the pathogenicity of Dpl and PrPΔCD in transgenic mice. The PrP-Dpl chimeric molecules, but not anchorless PrPΔCD, ameliorated the disease of mice expressing truncated PrP variants. We conclude that the amino proximal domain of PrP exerts a neurotrophic effect even when grafted onto a distantly related protein, and that GPI-linked membrane anchoring is necessary for both beneficial and deleterious effects of PrP and its variants

Modern Clinical Research on LSD

All modern clinical studies using the classic hallucinogen lysergic acid diethylamide (LSD) in healthy subjects or patients in the last 25 years are reviewed herein. There were five recent studies in healthy participants and one in patients. In a controlled setting, LSD acutely induced bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences. These subjective effects of LSD were mediated by the 5-HT2A receptor. LSD increased feelings of closeness to others, openness, trust, and suggestibility. LSD impaired the recognition of sad and fearful faces, reduced left amygdala reactivity to fearful faces, and enhanced emotional empathy. LSD increased the emotional response to music and the meaning of music. LSD acutely produced deficits in sensorimotor gating, similar to observations in schizophrenia. LSD had weak autonomic stimulant effects and elevated plasma cortisol, prolactin, and oxytocin levels. Resting-state functional magnetic resonance studies showed that LSD acutely reduced the integrity of functional brain networks and increased connectivity between networks that normally are more dissociated. LSD increased functional thalamocortical connectivity and functional connectivity of the primary visual cortex with other brain areas. The latter effect was correlated with subjective hallucinations. LSD acutely induced global increases in brain entropy that were associated with greater trait openness 14 days later. In patients with anxiety associated with life-threatening disease, anxiety was reduced for 2 months after two doses of LSD. In medical settings, no complications of LSD administration were observed. These data should contribute to further investigations of the therapeutic potential of LSD in psychiatry

Uncovering the multifaceted roles played by neutrophils in allogeneic hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a life-saving procedure used for the treatment of selected hematological malignancies, inborn errors of metabolism, and bone marrow failures. The role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against infection. However, recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered functions. Accordingly, neutrophils are emerging as highly versatile cells that are able to acquire different, often opposite, functional capacities depending on the microenvironment and their differentiation status. Herein, we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT, from the hematopoietic stem cell (HSC) mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC infusion. We also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versus-host disease (GVHD) prophylaxis. Finally, the potential involvement of neutrophils in alloHSCT-related complications, such as transplant-associated thrombotic microangiopathy (TA-TMA), acute and chronic GVHD, and cytomegalovirus (CMV) reactivation, is also discussed. Based on the data reviewed herein, the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial role. However, much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT

Analysis of Epstein-Barr virus reservoirs in paired blood and breast cancer primary biopsy specimens by real time PCR

INTRODUCTION: Epstein-Barr virus (EBV) is present in over 90% of the world's population. This infection is considered benign, even though in limited cases EBV is associated with infectious and neoplastic conditions. Over the past decade, the EBV association with breast cancer has been constantly debated. Adding to this clinical and biological uncertainty, different techniques gave contradictory results for the presence of EBV in breast carcinoma specimens. In this study, minor groove binding (MGB)-TaqMan real time PCR was used to detect the presence of EBV DNA in both peripheral blood and tumor samples of selected patients. METHODS: Peripheral blood and breast carcinoma specimens from 24 patients were collected. DNA was extracted and then amplified by MGB-TaqMan real time PCR. RESULTS: Of 24 breast tumor specimens, 11 (46%) were positive for EBV DNA. Of these 11 breast tumor specimens, 7 (64%) were also positive for EBV DNA in the peripheral blood, while 4 (36%) were positive for EBV DNA in the tumor, but negative in the blood. CONCLUSION: EBV was found at extremely low levels, with a mean of 0.00004 EBV genomes per cell (range 0.00014 to 0.00001 EBV genomes per cell). Furthermore, our finding of the presence of EBV in the tumor specimens coupled to the absence of detection of EBV genomic DNA in the peripheral blood is consistent with the epithelial nature of the virus. Because of the low levels of viral DNA in tumor tissue, further studies are needed to assess the biological input of EBV in breast cancer

Spatial and Temporal Patterns of Pore Water Chemistry in the Inter-Tidal Zone of a High Energy Beach

Submarine groundwater discharge (SGD) is a ubiquitous source of meteoric fresh groundwater and recirculating seawater to the coastal ocean. Due to the hidden distribution of SGD, as well as the hydraulic- and stratigraphy-driven spatial and temporal heterogeneities, one of the biggest challenges to date is the correct assessment of SGD-driven constituent fluxes. Here, we present results from a 3-dimensional seasonal sampling campaign of a shallow subterranean estuary in a high-energy, meso-tidal beach, Spiekeroog Island, Northern Germany. We determined beach topography and analyzed physico-chemical and biogeochemical parameters such as salinity, temperature, dissolved oxygen, Fe(II) and dissolved organic matter fluorescence (FDOM). Overall, the highest gradients in pore water chemistry were found in the cross-shore direction. In particular, a strong physico-chemical differentiation between the tidal high water and low water line was found and reflected relatively stable in- and exfiltrating conditions in these areas. Contrastingly, in between, the pore water compositions in the existing foreshore ridge and runnel system were very heterogeneous on a spatial and temporal scale. The reasons for this observation may be the strong morphological changes that occur throughout the entire year, which affect the exact locations and heights of the ridge and runnel structures and associated flow paths. Further, seasonal changes in temperature and inland hydraulic head, and the associated effect on microbial mediated redox reactions likely overprint these patterns. In the long-shore direction the pore water chemistry varied less than the along the cross-shore direction. Variation in long-shore direction was probably occurring due to topography changes of the ridge-runnel structure and a physical heterogeneity of the sediment, which produced non-uniform groundwater flow conditions. We conclude that on meso-tidal high energy beaches, the rapidly changing beach morphology produces zones with different approximations to steady-state conditions. Therefore, we suggest that zone-specific endmember sampling is the optimal strategy to reduce uncertainties of SGD-driven constituent fluxes