This nesting burrow may provide a search image for more fossil iguana burrows in The Bahamas and other places with long-established iguana species and favorable geological conditions for preserving their burrows.G Protein-Coupled Receptors (GPCRs) mediate intracellular signaling in response to extracellular ligand binding and are the target of one-third of approved drugs. Ligand binding modulates the GPCR molecular free energy landscape by preferentially stabilizing active or inactive conformations that dictate intracellular protein recruitment and downstream signaling. We perform enhanced sampling molecular dynamics simulations to recover the free energy surfaces of a thermostable mutant of the GPCR serotonin receptor 5-HT2B in the unliganded form and bound to a lysergic acid diethylamide (LSD) agonist and lisuride antagonist. LSD binding imparts a ∼110 kJ/mol driving force for conformational rearrangement into an active state. The lisuride-bound form is structurally similar to the apo form and only ∼24 kJ/mol more stable. This work quantifies ligand-induced conformational specificity and functional selectivity of 5-HT2B and presents a platform for high-throughput virtual screening of ligands and rational engineering of the ligand-bound molecular free energy landscape.Estimation of the postmortem interval in advanced postmortem stages is a challenging task. Although there are several approaches available for addressing postmortem changes of a (human) body or its environment (ecologically and/or biochemically), most are restricted to specific timeframes and/or individual and environmental conditions. It is well known, for instance, that buried bodies decompose in a remarkably different manner than on the ground surface. However, data on how established methods for PMI estimation perform under these conditions are scarce. It is important to understand whether and how postmortem changes are affected under burial conditions, if corrective factors could be conceived, or if methods have to be excluded for respective cases. We present the first multi-methodological assessment of human postmortem decomposition carried out on buried body donors in Europe, at the Amsterdam Research Initiative for Sub-surface Taphonomy and Anthropology (ARISTA) in the Netherlands. We used a multidisciplinary approach to investigate postmortem changes of morphology, skeletal muscle protein decomposition, presence of insects and other necrophilous animals as well as microbial communities (i.e., microbiomes) from August to November 2018 associated with two complete body exhumations and eight partial exhumations. Our results clearly display the current possibilities and limitations of methods for PMI estimation in buried remains and provide a baseline for future research and application.Carbonic anhydrase-IX (CA-IX) is attracting much attention as a target molecule for cancer treatment since high expression of CA-IX can lead to a poor prognosis of patients. We previously reported low-molecular-weight 111In/90Y complexes with a bivalent ureidosulfonamide scaffold ([111In/90Y]In/Y-US2) as cancer radiotheranostic agents for single photon emission computed tomography and radionuclide-based therapy targeting CA-IX. Here, we applied the US2 platform to positron emission tomography (PET) imaging and pharmacological therapy targeting CA-IX high-expressing tumors by introducing 68Ga and natIn, respectively. In an in vitro cell binding assay, [67Ga]Ga-US2, an alternative complex of [68Ga]Ga-US2 with a longer half-life, markedly bound to CA-IX high-expressing (HT-29) cells compared with low-expressing (MDA-MB-231) cells. In a biodistribution study with HT-29 and MDA-MB-231 tumor-bearing mice, [67Ga]Ga-US2 showed accumulation in the HT-29 tumor (3.81% injected dose/g at 60 min postinjection) and clearance from the blood pool with time. PET with [68Ga]Ga-US2 clearly visualized the HT-29 tumor in model mice at 60 min postinjection. In addition, the administration of [natIn]In-US2 to HT-29 tumor-bearing mice led to tumor growth delay and prolonged mouse survival, while no critical toxicity was observed. These results indicate that [68Ga]Ga-US2 and [natIn]In-US2 may be useful imaging and therapeutic agents targeting CA-IX, respectively, and that US2 may serve as an effective cancer theranostic platform utilizing CA-IX.The signal peptides, present at the N-terminus of many proteins, guide the proteins into cell membranes. In some proteins, the signal peptide is with an extended N-terminal region. Previously, it was demonstrated that the N-terminally extended signal peptide of the human PTPRJ contains a cluster of arginine residues, which attenuates translation. The analysis of the mammalian orthologous sequences revealed that this sequence is highly conserved. The PTPRJ transcripts in placentals, marsupials, and monotremes encode a stretch of 10-14 arginine residues, positioned 11-12 codons downstream of the initiating AUG. The remarkable conservation of the repeated arginine residues in the PTPRJ signal peptides points to their key role. Further, the presence of an arginine cluster in the extended signal peptides of other proteins (E3 ubiquitin-protein ligase, NOTCH3) is noted and indicates a more general importance of this cis-acting mechanism of translational suppression.The complexity of Neolithic population movements and their interpretation through material culture have been the subject of archaeological research for decades. One of the dominant narratives proposes that groups from the Starčevo-Körös-Criş complex spread from the central towards the northern Balkans in the Early Neolithic and eventually brought the Neolithic lifestyle into present-day Hungary.  https://www.selleckchem.com/products/motolimod-vtx-2337.html  Broad geographical migrations were considered to shape the continuous expansion of Neolithic groups and individuals. However, recent archaeological research, aDNA, and isotope analyses challenged the synchronous appearance of specific material culture distributions and human movement dynamics through emphasizing communication networks and socio-cultural transformation processes. This paper seeks to retrace the complexity of Neolithic mobility patterns across Hungary by means of strontium and oxygen stable isotope analyses, which were performed on a total of 718 human dental enamel samples from 55 Neolithic sites spanning the period from the Starčevo to the Balaton-Lasinja culture in Transdanubia and from the Körös to the Tiszapolgár cultural groups on the Great Hungarian Plain (Alföld).