Spatio-temporal variations of climate along possible African-Arabian routes of H. sapiens expansion

Eastern Africa and Arabia were major hominin hotspots and critical crossroads for migrating towards Asia during the late Pleistocene. To decipher the role of spatiotemporal environmental change on human occupation and migration patterns, we remeasured the marine core from Meteor Site KL 15 in the Gulf of Aden and reanalyzed its data together with the aridity index from ICDP Site Chew Bahir in eastern Africa and the wet-dry index from ODP Site 967 in the eastern Mediterranean Sea using linear and nonlinear time series analysis. These analyses show major changes in the spatiotemporal paleoclimate dynamics at 400 and 150 ka BP (thousand years before 1950), presumably driven by changes in the amplitude of the orbital eccentricity. From 400 to 150 ka BP, eastern Africa and Arabia show synchronized wet-dry shifts, which changed drastically at 150 ka BP. After 150 ka BP, an overall trend to dry climate states is observable, and the hydroclimate dynamics between eastern Africa and Arabia are negatively correlated. Those spatio-temporal variations and interrelationships of climate potentially influenced the availability of spatial links for human expansion along those vertices. We observe positively correlated network links during the supposed out-of-Africa migration phases of H. sapiens. Furthermore, our data do not suggest hominin occupation phases during specific time intervals of humid or stable climates but provide evidence of the so far underestimated potential role of climate predictability as an important factor of hominin ecological competitiveness

Case Report: A Case of Severe Clinical Deterioration in a Patient With Multiple Sclerosis

Tumefactive multiple sclerosis (MS) is a rare variant of MS that may lead to a rapidly progressive clinical deterioration requiring a multidisciplinary diagnostic workup. Our report describes the diagnostic and therapeutic approach of a rare and extremely severe course of MS. A 51-year-old man with an 8-year history of relapsing-remitting MS (RRMS) was admitted with a subacute progressive left lower limb weakness and deterioration of walking ability. After extensive investigations including repeated MRI, microbiological, serological, cerebrospinal fluid (CSF) studies, and finally brain biopsy, the diagnosis of a tumefactive MS lesion was confirmed. Despite repeated intravenous (IV) steroids as well as plasma exchanges and IV foscarnet and ganciclovir owing to low copy numbers of human herpesvirus 6 (HHV-6) DNA in polymerase chain reaction (PCR) analysis, the patient did not recover. The clinical presentation of tumefactive MS is rare and variable. Brain biopsy for histopathological workup should be considered in immunocompromised patients with rapidly progressive clinical deterioration with brain lesions of uncertain cause

The Phase Diagram and Spectrum of Gauge-Fixed Abelian Lattice Gauge Theory

We consider a lattice discretization of a covariantly gauge-fixed abelian gauge theory. The gauge fixing is part of the action defining the theory, and we study the phase diagram in detail. As there is no BRST symmetry on the lattice, counterterms are needed, and we construct those explicitly. We show that the proper adjustment of these counterterms drives the theory to a new type of phase transition, at which we recover a continuum theory of (free) photons. We present both numerical and (one-loop) perturbative results, and show that they are in good agreement near this phase transition. Since perturbation theory plays an important role, it is important to choose a discretization of the gauge-fixing action such that lattice perturbation theory is valid. Indeed, we find numerical evidence that lattice actions not satisfying this requirement do not lead to the desired continuum limit. While we do not consider fermions here, we argue that our results, in combination with previous work, provide very strong evidence that this new phase transition can be used to define abelian lattice chiral gauge theories.Comment: 42 pages, 30 figure

Chiral Fermions on the Lattice through Gauge Fixing -- Perturbation Theory

We study the gauge-fixing approach to the construction of lattice chiral gauge theories in one-loop weak-coupling perturbation theory. We show how infrared properties of the gauge degrees of freedom determine the nature of the continuous phase transition at which we take the continuum limit. The fermion self-energy and the vacuum polarization are calculated, and confirm that, in the abelian case, this approach can be used to put chiral gauge theories on the lattice in four dimensions. We comment on the generalization to the nonabelian case.Comment: 31 pages, 5 figures, two refs. adde

Attenuated PDGF signaling drives alveolar and microvascular defects in neonatal chronic lung disease

Neonatal chronic lung disease (nCLD) affects a significant number of neonates receiving mechanical ventilation with oxygen-rich gas (MV-O2). Regardless, the primary molecular driver of the disease remains elusive. We discover significant enrichment for SNPs in the PDGF-Rα gene in preterms with nCLD and directly test the effect of PDGF-Rα haploinsufficiency on the development of nCLD using a preclinical mouse model of MV-O2. In the context of MV-O2, attenuated PDGF signal

Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents

Antigen-specific tissue-resident memory T cells (Trms) and neutralizing IgA antibodies provide the most effective protection of the lungs from viral infections. To induce those essential components of lung immunity against SARS-CoV-2, we tested various immunization protocols involving intranasal delivery of a novel Modified Vaccinia virus Ankara (MVA)-SARS-2-spike vaccine candidate. We show that a single intranasal MVA-SARS-CoV-2-S application in mice strongly induced pulmonary spike-specific CD8+ T cells, albeit restricted production of neutralizing antibodies. In prime-boost protocols, intranasal booster vaccine delivery proved to be crucial for a massive expansion of systemic and lung tissue-resident spike-specific CD8+ T cells and the development of Th1 - but not Th2 - CD4+ T cells. Likewise, very high titers of IgG and IgA anti-spike antibodies were present in serum and broncho-alveolar lavages that possessed high virus neutralization capacities to all current SARS-CoV-2 variants of concern. Importantly, the MVA-SARS-2-spike vaccine applied in intramuscular priming and intranasal boosting treatment regimen completely protected hamsters from developing SARS-CoV-2 lung infection and pathology. Together, these results identify intramuscular priming followed by respiratory tract boosting with MVA-SARS-2-S as a promising approach for the induction of local, respiratory as well as systemic immune responses suited to protect from SARS-CoV-2 infections

Large-Scale Imputation of KIR Copy Number and HLA Alleles in North American and European Psoriasis Case-Control Cohorts Reveals Association of Inhibitory KIR2DL2 With Psoriasis

Killer cell immunoglobulin-like receptors (KIR) regulate immune responses in NK and CD8+ T cells via interaction with HLA ligands. KIR genes, including KIR2DS1, KIR3DL1, and KIR3DS1 have previously been implicated in psoriasis susceptibility. However, these previous studies were constrained to small sample sizes, in part due to the time and expense required for direct genotyping of KIR genes. Here, we implemented KIR*IMP to impute KIR copy number from single-nucleotide polymorphisms (SNPs) on chromosome 19 in the discovery cohort (n=11,912) from the PAGE consortium, University of California San Francisco, and the University of Dundee, and in a replication cohort (n=66,357) from Kaiser Permanente Northern California. Stratified multivariate logistic regression that accounted for patient ancestry and high-risk HLA alleles revealed that KIR2DL2 copy number was significantly associated with psoriasis in the discovery cohort (p ≤ 0.05). The KIR2DL2 copy number association was replicated in the Kaiser Permanente replication cohort. This is the first reported association of KIR2DL2 copy number with psoriasis and highlights the importance of KIR genetics in the pathogenesis of psoriasis

Probing intermediates in the activation cycle of [NiFe] hydrogenase by infrared spectroscopy: the Ni-SIr state and its light sensitivity

The [NiFe] hydrogenase from the sulphate-reducing bacterium Desulfovibrio vulgaris Miyazaki F is reversibly inhibited in the presence of molecular oxygen. A key intermediate in the reactivation process, Ni-SIr, provides the link between fully oxidized (Ni-A, Ni-B) and active (Ni-SIa, Ni-C and Ni-R) forms of hydrogenase. In this work Ni-SIr was found to be light-sensitive (T ≤ 110 K), similar to the active Ni-C and the CO-inhibited states. Transition to the final photoproduct state (Ni-SL) was shown to involve an additional transient light-induced state (Ni-SI1961). Rapid scan kinetic infrared measurements provided activation energies for the transition from Ni-SL to Ni-SIr in protonated as well as in deuterated samples. The inhibitor CO was found not to react with the active site of the Ni-SL state. The wavelength dependence of the Ni-SIr photoconversion was examined in the range between 410 and 680 nm. Light-induced effects were associated with a nickel-centred electronic transition, possibly involving a change in the spin state of nickel (Ni2+). In addition, at T ≤ 40 K the CN− stretching vibrations of Ni-SL were found to be dependent on the colour of the monochromatic light used to irradiate the species, suggesting a change in the interaction of the hydrogen-bonding network of the surrounding amino acids. A possible mechanism for the photochemical process, involving displacement of the oxygen-based ligand, is discussed

Epitaxial monolayers of the magnetic 2D semiconductor FeBr2 grown on Au(111)

Magnetic two-dimensional (2D) semiconductors have attracted a lot of attention because modern preparation techniques are capable of providing single-crystal films of these materials with precise control of thickness down to the single-layer limit. It opens up a way to study a rich variety of electronic and magnetic phenomena with promising routes toward potential applications. We have investigated the initial stages of epitaxial growth of the magnetic van der Waals semiconductor FeBr2 on a single-crystal Au(111) substrate by means of low-temperature scanning tunneling microscopy (STM), low-energy electron diffraction (LEED), X-ray photoemission spectroscopy (XPS), low-energy electron emission microscopy (LEEM), and X-ray photoemission electron microscopy (XPEEM). Magnetic properties of the one- and two-layer thick films were measured via X-ray absorption spectroscopy (XAS) and X-ray magnetic circular dichroism (XMCD). Our findings show a striking difference in the magnetic behavior of the single layer of FeBr2 and its bulk counterpart, which can be attributed to the modifications in the crystal structure due to the interaction with the substrate.C.G.-O. and M.P.-D. acknowledge funding of the Ph.D. fellowship from the MPC Foundation. S.E.H. thanks the whole AG Kuch and in particular J. Gördes for help during the BESSY measurements and also the local IT/electronics workshop/fine mechanics workshop teams for their continuous support. In particular, he is very thankful for the possibility to perform some last STM measurements at the PEARL beamline at SLS thanks Dr. Matthias Muntwiler. J.N. thanks the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) for his funding under project 277101999 - CRC 183. S.T. acknowledges financial support by BMBF through project VEKMAG (BMBF 05K19KEA). P.G. acknowledges funding from PID2020-116181RB-C32 and FlagEraSOgraphMEM PCI2019-111908-2 (AEI/FEDER). D.G.O. acknowledges funding by the Spanish MCIN/AEI/10.13039/501100011033 and by the European Union “NextGenerationEU”/PRTR (PID2019-107338RB-C63 and TED2021-132388B–C43). C.R., M.I., C.G.-O., and M.P.-D. acknowledge funding by the European Union’s Horizon 2020 research and innovation program (grant agreement No 800923), the Spanish MCIN/AEI/10.13039/501100011033 (PID2020-114252GB-I00, PID2019-107338RB-C63, TED2021-130292B–C42), the Basque Goverment IT1591-22, and by the IKUR Strategy under the collaboration agreement between Ikerbasque Foundation and MPC on behalf of the Department of Education of the Basque Government. C.R., M.I., C.G.-O., and S.E.H. are very thankful for the help during the XMCD and STM measurements of Samuel Kerschbaumer, Andrea Aguirre Baños, and Amitayush Jha Thakur.Peer reviewe