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The precise genetic origins of the first Neolithic farming populations in Europe and Southwest Asia, as well as the processes and the timing of their differentiation, remain largely unknown. Demogenomic modeling of high-quality ancient genomes reveals that the early farmers of Anatolia and Europe emerged from a multiphase mixing of a Southwest Asian population with a strongly bottlenecked western hunter-gatherer population after the last glacial maximum. Moreover, the ancestors of the first farmers of Europe and Anatolia went through a period of extreme genetic drift during their westward range expansion, contributing highly to their genetic distinctiveness. This modeling elucidates the demographic processes at the root of the Neolithic transition and leads to a spatial interpretation of the population history of Southwest Asia and Europe during the late Pleistocene and early Holocene., Cell, 185 (11), ISSN:0092-8674, ISSN:1097-4172

Endogenous retroviruses (ERVs) are an integral part of the mammalian genome. The role of immune control of ERVs in general is poorly defined as is their role as anti-cancer immune targets or drivers of autoimmune disease. Here, we generated mouse-strains where Moloney-Murine Leukemia Virus tagged with GFP (ERV-GFP) infected the murine germline. This enabled us to analyze the role of genetic, epigenetic and cell intrinsic restriction factors in ERV activation and control. We identified an autoreactive B cell response against the neo-self/ERV antigen GFP as a key mechanism of ERV control. Hallmarks of this response are spontaneous ERV-GFP+ germinal center formation, elevated serum IFN-γ levels and a dependency on T-bet+ B cells. Impairment of IgM B cell receptor-signal in nucleic-acid sensing TLR-deficient mice contributes to defective ERV control. Although ERVs are a part of the genome they break immune tolerance, induce immune surveillance against ERV-derived self-antigens and shape the hosts immune response.

Preparation of Amplicons for deep sequencing is based on two PCR steps. The genomic loci of interest is enriched in a first PCR including a stubber sequence to both ends of the molecule. For the subsequent barcoding PCR the stubber sequence is targeted and the full NGS sequencing adapter including dual barcodes are introduced to the molecule ends, enabling Illumina sequencing on all instruments. By default we recommend a 150 PE sequencing workflow and amplicon size including the specific primer binding sites should not extend 280bp. Schematic overview

Most known pathogenic point mutations in humans are C center dot G to T center dot A substitutions, which can be directly repaired by adenine base editors (ABEs). In this study, we investigated the efficacy and safety of ABEs in the livers of mice and cynomolgus macaques for the reduction of blood low-density lipoprotein (LDL) levels. Lipid nanoparticle-based delivery of mRNA encoding an ABE and a single-guide RNA targeting PCSK9, a negative regulator of LDL, induced up to 67% editing (on average, 61%) in mice and up to 34% editing (on average, 26%) in macaques. Plasma PCSK9 and LDL levels were stably reduced by 95% and 58% in mice and by 32% and 14% in macaques, respectively. ABE mRNA was cleared rapidly, and no off-target mutations in genomic DNA were found. Re-dosing in macaques did not increase editing, possibly owing to the detected humoral immune response to ABE upon treatment. These findings support further investigation of ABEs to treat patients with monogenic liver diseases., Base editors are effective and safe for cholesterol reduction in non-human primates., Nature Biotechnology, 39 (8), ISSN:1546-1696, ISSN:1087-0156

The treatment of non-small cell lung cancer (NSCLC) patients with immune checkpoint inhibitors has prolonged their survival dramatically. However, some patients develop resistance after initial response. Here, we used imaging mass cytometry and whole exome and RNA sequencing to analyze matching tumor samples from a cohort of NSCLC patients who initially responded to immune checkpoint inhibitor therapy and later developed acquired resistance. We detected two patterns of resistance: One group of patients had reduced numbers of tumor-infiltrating CD8+ T cells and reduced expression of PD-L1 after development of resistance, whereas the other group showed high CD8+ T cell infiltration and high expression of PD-L1 and markedly elevated expression of other immune-inhibitory molecules. In two cases, we detected downregulation of type I and II IFN pathways after resistance developed, which could lead to an impaired anti-tumor immune response. This study adds to our knowledge of the mechanisms that cause resistance to immunotherapy in NSCLC patients.

Prime editing is a highly versatile CRISPR-based genome editing technology that works without DNA double-strand break formation. Despite rapid technological advances, in vivo application for the treatment of genetic diseases remains challenging. Here, we developed a size-reduced Sp Cas9 prime editor (PE) lacking the RNaseH domain (PE2 Δ RnH ) and an intein-split construct (PE2 p.1153) for adeno-associated virus–mediated delivery into the liver. Editing efficiencies reached 15% at the Dnmt1 locus and were further elevated to 58% by delivering unsplit PE2 Δ RnH via human adenoviral vector 5 (AdV). To provide proof of concept for correcting a genetic liver disease, we used the AdV approach for repairing the disease-causing Pah enu2 mutation in a mouse model of phenylketonuria (PKU) via prime editing. Average correction efficiencies of 11.1% (up to 17.4%) in neonates led to therapeutic reduction of blood phenylalanine, without inducing detectable off-target mutations or prolonged liver inflammation. Although the current in vivo prime editing approach for PKU has limitations for clinical application due to the requirement of high vector doses (7 × 10 14 vg/kg) and the induction of immune responses to the vector and the PE, further development of the technology may lead to curative therapies for PKU and other genetic liver diseases.

Knowledge about the age of a stain, also termed as time since deposition (TsD), would provide law-enforcing authorities with valuable information for the prosecution of criminal offenses. Yet, there is no reliable method for the inference / assessment of TsD available. The aim of this study was to gain further insight into the RNA degradation pattern of forensically relevant body fluids and to find candidate markers for TsD estimation. Blood, menstrual blood, saliva, semen and vaginal secretion samples were exposed to indoor (dark, room temperature) and outdoor (exposed to sun, wind, etc. but protected from rain) conditions for up to 1.5 years. Based on expression and degradation analyses, we were able to identify body fluid specific signatures and RNA degradation patterns. The indoor samples showed a marked drop in RNA integrity after 6 months, while the outdoor samples were difficult to interpret and therefore excluded for some of the analyses. Up to 4 weeks, indoor samples showed more stable and less degrading transcripts than outdoor samples. Stable transcripts tended to be significantly shorter than degrading ones or transcripts, which are neither degrading nor stable. We reinforced the body fluid specific and the housekeeping gene nature of previously reported markers. With an unbiased approach, we selected stable and degrading genes for each body fluid in the short term and assessed their integrity during extended storage. We identified several stable and degrading gene transcripts, which could be tested in a targeted assay to assess the TsD interval e.g. by analyzing the ratio of degrading vs stable transcripts. In conclusion, we were able to detect RNA degradation patterns in samples being aged up to 1.5 years and identified several candidate markers, which could be evaluated for TsD estimation. ISSN:1872-4973 ISSN:1878-0326

Current body fluid identification methods do not reveal any information about the time since deposition (TsD) of biological traces, even though determining the age of traces could be crucial for the investigative process. To determine the utility of microbial RNA markers for TsD estimation, we examined RNA sequencing data from five forensically relevant body fluids (blood, menstrual blood, saliva, semen, and vaginal secretion) over seven time points, ranging from fresh to 1.5 years. One set of samples was stored indoors while another was exposed to outdoor conditions. In outdoor samples, we observed a consistent compositional shift, occurring after 4 weeks: this shift was characterized by an overall increase in non-human eukaryotic RNA and an overall decrease in prokaryotic RNA. In depth analyses showed a high fraction of tree, grass and fungal signatures, which are characteristic for the environment the samples were exposed to. When examining the prokaryotic fraction in more detail, three bacterial phyla were found to exhibit the largest changes in abundance, namely Actinobacteria, Proteobacteria and Firmicutes. More detailed analyses at the order level were done using a Lasso regression analysis to find a predictive subset of bacterial taxa. We found 26 bacterial orders to be indicative of sample age. Indoor samples did not reveal such a clear compositional change at the domain level: eukaryotic and prokaryotic abundance remained relatively stable across the assessed time period. Nonetheless, a Lasso regression analysis identified 32 bacterial orders exhibiting clear changes over time, enabling the prediction of TsD. For both indoor and outdoor samples, a larger number (around 60%) of the bacterial orders identified as indicative of TsD are part of the Actinobacteria, Proteobacteria and Firmicutes. In summary, we found that the observed changes across time are not primarily due to changes associated with body fluid specific bacteria but mostly due to accumulation of bacteria from the environment. Orders of these environmental bacteria could be evaluated for TsD prediction, considering the location and environment of the crime scene. However, further studies are needed to verify these findings, determine the applicability across samples, replicates, donors, and other variables, and also to further assess the effect of different seasons and locations on the samples. ISSN:1872-4973 ISSN:1878-0326

Necrotizing gingivitis (NG) is a necrotizing periodontal disease that differs from chronic gingivitis (CG). To date, both the microbiological causes and the involved host cytokine response of NG still remain unclear. Here, we investigated corresponding interdental plaque and serum samples from two groups of Chinese patients with CG (n = 21) or NG (n = 21). The microbiota were studied by 16S rRNA Illumina MiSeq sequencing of the microbial metagenome and by assessing quantitatively the abundance of the phylum Bacteroidetes, the genus Prevotella and the species T. forsythia, P. endodon-talis, and P. gingivalis using fluorescence in situ hybridization (FISH). With respect to the associated host response, the levels of 30 inflammatory mediators were quantified by multiplex immunoassay analysis. Differential microbial abundance analysis of the two disease groups revealed at the phylum level that Proteobacteria accounted for 67% of the differentially abundant organisms, followed by organisms of Firmicutes (21%) and Actinobacteria (9%). At the species level, significant differences in abundance were seen for 75 species of which 58 species were significantly more abundant in CG patients. Notably, the FISH analysis revealed that Bacteroidetes was the most prevalent phylum in NG. The multiplex cytokine assay showed significant quantitative differences between the disease groups for eight analytes (GM–CSF, G–CSF, IFN–α, IL–4, IL–13, TNF–α, MIG, and HGF). The G–CSF was found to be the most significantly increased inflammatory protein marker in NG. The next-generation sequencing (NGS) data supported the understanding of NG as a multi-microbial infection with distinct differences to CG in regard to the microbial composition., Antibiotics, 10 (10), ISSN:2079-6382

The precise genetic origins of the first Neolithic farming populations, as well as the processes and the timing of their differentiation, remain largely unknown. Based on demogenomic modeling of high-quality ancient genomes, we show that the early farmers of Anatolia and Europe emerged from a multiphase mixing of a Near Eastern population with a strongly bottlenecked Western hunter-gatherer population after the Last Glacial Maximum. Moreover, the population branch leading to the first farmers of Europe and Anatolia is characterized by a 2,500-year period of extreme genetic drift during its westward range expansion. Based on these findings, we derive a spatially explicit model of the population history of Southwest Asia and Europe during the late Pleistocene and early Holocene.One-Sentence Summary:Early European farmers emerged from multiple post LGM mixtures and experienced extreme drift during their westward expansion.

The recent outbreak of a new coronavirus that causes a Severe Acute Respiratory Syndrome in humans (SARS-CoV-2) has developed into a global pandemic with over 6 million reported cases and more than 375,000 deaths worldwide. Many countries have faced a shortage of diagnostic kits as well as a lack of infrastructure to perform necessary testing. Due to these limiting factors, only patients showing symptoms indicating infection were subjected to testing, whilst asymptomatic individuals, who are widely believed to be responsible for the fast dispersion of the virus, were largely omitted from the testing regimes. The inability to implement high throughput diagnostic and contact tracing strategies has forced many countries to institute lockdowns with severe economic and social consequences. The World Health Organization (WHO) has encouraged affected countries to increase testing capabilities to identify new cases, allow for a well-controlled lifting of lockdown measures, and prepare for future outbreaks. Here, we propose HiDRA-seq, a rapidly implementable, high throughput, and scalable solution that uses NGS lab infrastructure and reagents for population-scale SARS-CoV-2 testing. This method is based on the use of indexed oligo-dT primers to generate barcoded cDNA from a large number of patient samples. From this, highly multiplexed NGS libraries are prepared targeting SARS-CoV-2 specific regions and sequenced. The low amount of sequencing data required for diagnosis allows the combination of thousands of samples in a sequencing run, while reducing the cost to approximately 2 CHF/EUR/USD per RNA sample. Here, we describe in detail the first version of the protocol, which can be further improved in the future to increase its sensitivity and to identify other respiratory viruses or analyze individual genetic features associated with disease progression.

Funder: FP7 Ideas: European Research Council; funder-id: http://dx.doi.org/10.13039/100011199; Grant(s): 295729, The recovery and analysis of ancient DNA and protein from archaeological bone is time-consuming and expensive to carry out, while it involves the partial or complete destruction of valuable or rare specimens. The fields of palaeogenetic and palaeoproteomic research would benefit greatly from techniques that can assess the molecular quality prior to sampling. To be relevant, such screening methods should be effective, minimally-destructive, and rapid. This study reports results based on spectroscopic (Fourier-transform infrared spectroscopy in attenuated total reflectance [FTIR-ATR]; n = 266), palaeoproteomic (collagen content; n = 226), and palaeogenetic (endogenous DNA content; n = 88) techniques. We establish thresholds for three different FTIR indices, a) the infrared splitting factor [IRSF] that assesses relative changes in bioapatite crystals’ size and homogeneity; b) the carbonate-to-phosphate [C/P] ratio as a relative measure of carbonate content in bioapatite crystals; and c) the amide-to-phosphate ratio [Am/P] for assessing the relative organic content preserved in bone. These thresholds are both extremely reliable and easy to apply for the successful and rapid distinction between well- and poorly-preserved specimens. This is a milestone for choosing appropriate samples prior to genomic and collagen analyses, with important implications for biomolecular archaeology and palaeontology.

Background & Aims Although hepatitis E constitutes a substantial disease burden worldwide, surprisingly little is known about the localization of hepatitis E virus (HEV) in the human liver. We therefore aimed to visualize HEV RNA and proteins in situ . Methods A panel of 12 different antibodies against HEV open reading frame (ORF) 1–3 proteins was evaluated for immunohistochemistry (IHC) and two probes for in situ hybridization (ISH) in formalin-fixed, paraffin-embedded (FFPE) HuH7 cells transfected with HEV ORF1-3 expression vectors. IHC (and partly ISH) were then applied to Hep293TT cells replicating infectious HEV and liver specimens from patients with hepatitis E (n=20) and controls (n=134). Results Whereas ORF1-3 proteins were all detectable in transfected, HEV protein-expressing cells, only ORF2 and 3 proteins were traceable in cells replicating infectious HEV. Only the ORF2-encoded capsid protein was also unequivocally detectable in liver specimens from patients with hepatitis E. IHC for ORF2 protein revealed a patchy expression in individual or grouped hepatocytes, generally stronger in chronic compared to acute hepatitis. Besides cytoplasmic and canalicular, ORF2 protein also displayed a hitherto unknown nuclear localization. Positivity for ORF2 protein in defined areas correlated with HEV RNA detection by ISH. IHC was specific and comparably sensitive as PCR for HEV RNA. Conclusions ORF2 protein can be reliably visualized in the liver of patients with hepatitis E, allowing for sensitive and specific detection of HEV in FFPE samples. Its variable subcellular distribution in individual hepatocytes of the same liver suggests a redistribution of ORF2 protein during infection and interaction with nuclear components. Lay summary The open reading frame (ORF) 2 protein can be used to visualize the hepatitis E virus (HEV) in the human liver. This enabled us to discover a hitherto unknown localization of the HEV ORF2 protein in the nucleus of hepatocytes and to develop a test for rapid histopathologic diagnosis of hepatitis E, the most common cause of acute hepatitis worldwide.

Background & Aims Intestinal epithelial homeostasis depends on a tightly regulated balance between intestinal epithelial cell (IEC) death and proliferation. While the disruption of several IEC death regulating factors result in intestinal inflammation, the loss of the anti-apoptotic BCL2 family members BCL2 and BCL2L1 has no effect on intestinal homeostasis in mice. We investigated the functions of the antiapoptotic protein MCL1, another member of the BCL2 family, in intestinal homeostasis in mice. Methods We generated mice with IEC-specific disruption of Mcl1 (Mcl1ΔIEC mice) or tamoxifen-inducible IEC-specific disruption of Mcl1 (i-Mcl1ΔIEC mice); these mice and mice with full-length Mcl1 (controls) were raised under normal or germ-free conditions. Mice were analyzed by endoscopy and for intestinal epithelial barrier permeability. Intestinal tissues were analyzed by histology, in situ hybridization, proliferation assays, and immunoblots. Levels of calprotectin, a marker of intestinal inflammation, were measured in intestinal tissues and feces. Results Mcl1ΔIEC mice spontaneously developed apoptotic enterocolopathy, characterized by increased IEC apoptosis, hyperproliferative crypts, epithelial barrier dysfunction, and chronic inflammation. Loss of MCL1 retained intestinal crypts in a hyperproliferated state and prevented the differentiation of intestinal stem cells. Proliferation of intestinal stem cells in MCL1-deficient mice required WNT signaling and was associated with DNA damage accumulation. By 1 year of age, Mcl1ΔIEC mice developed intestinal tumors with morphologic and genetic features of human adenomas and carcinomas. Germ-free housing of Mcl1ΔIEC mice reduced markers of microbiota-induced intestinal inflammation but not tumor development. Conclusion The antiapoptotic protein MCL1, a member of the BCL2 family, is required for maintenance of intestinal homeostasis and prevention of carcinogenesis in mice. Loss of MCL1 results in development of intestinal carcinomas, even under germ-free conditions, and therefore does not involve microbe-induced chronic inflammation. Mcl1ΔIEC mice might be used to study apoptotic enterocolopathy and inflammatory bowel diseases., Graphical abstract

The retrieval of ancient DNA from osteological material provides direct evidence of human genetic diversity in the past. Ancient DNA samples are often used to investigate whether there was population continuity in the settlement history of an area. Methods based on the serial coalescent algorithm have been developed to test whether the population continuity hypothesis can be statistically rejected by analysing DNA samples from the same region but of different ages. Rejection of this hypothesis is indicative of a large genetic shift, possibly due to immigration occurring between two sampling times. However, this approach is only able to reject a model of full continuity model (a total absence of genetic input from outside), but admixture between local and immigrant populations may lead to partial continuity. We have recently developed a method to test for population continuity that explicitly considers the spatial and temporal dynamics of populations. Here, we extended this approach to estimate the proportion of genetic continuity between two populations, using ancient genetic samples. We applied our original approach to the question of the Neolithic transition in Central Europe. Our results confirmed the rejection of full continuity, but our approach represents an important step forward by estimating the relative contribution of immigrant farmers and of local hunter‐gatherers to the final Central European Neolithic genetic pool. Furthermore, we show that a substantial proportion of genes brought by the farmers in this region were assimilated from other hunter‐gatherer populations along the way from Anatolia, which was not detectable by previous continuity tests. Our approach is also able to jointly estimate demographic parameters, as we show here by finding both low density and low migration rate for pre‐Neolithic hunter‐gatherers. It provides a useful tool for the analysis of the numerous ancient DNA data sets that are currently being produced for many different species.

L’ecole d’infirmiere de l’universite d’Heidelberg fut fondee en 1953 a l’initiative de la fondation Rockefeller pour former scientifiquement une nouvelle « elite du nursing », pionniere de la professionnalisation du corps infirmier en Republique federale d’Allemagne. Son concept « americain », percu comme formant des infirmieres « hollywoodiennes » elitistes, menacant l’idee traditionnelle chretienne d’un bon travail infirmier axe sur le care, provoqua une levee de boucliers et des tensions avec les autres groupes d’infirmieres, mais nombre des premieres professeures allemandes en sciences infirmieres y furent formees.

The School of Nursing at Heidelberg University was founded in 1953 on the initiative of the Rockefeller Foundation to generate new, scientifically trained nursing elite to advance the professionalization of nursing in West Germany. The "American" concept met massive resistance. Its "superior nursing training" was seen as creating "Hollywood nurses"-a threat to the traditional Christian understanding of good, caring nursing. Intense social conflicts also caused problems with other groups of nurses. The school nevertheless played a very important role as a "cadre academy" in the history of professionalization. Many of the first German professors in the nursing sciences trained or underwent further training in Heidelberg.West German nursing after World War II set no great store by theoretical instruction. A "good" nurse was primarily "good at heart," and tradition had it that a nurse's heart was educated by practical nursing tasks and being part of the community of sisters. Into the early 1950s West German nursing was influenced by the large confessional motherhouse sisterhoods and their tenets of Christian charity.1 Nurses spent most of their training time on the wards and learned the skills they needed, including their work ethics, from experienced colleagues. The lessons in the nursing school classrooms attached to the hospitals were of minor importance. This strong emphasis on practical experience did not only apply to basic nursing training. Head nurses and nursing teachers were qualified based on years of practical experience, not because they attended advanced training courses.2It was against this backdrop that an entirely new, academically oriented type of school was established in 1953 on the initiative of the Rockefeller Foundation and the American military government. The Heidelberg School of Nursing was affiliated with Heidelberg University's Medical School with the aim of generating a new nursing elite that would advance professionalization of nursing in West Germany. The Rockefeller Foundation initiated similar schools in many other countries.3 In founding the Heidelberg School, the Foundation wanted to promote its public health model-a unified community program focusing on the health of families in their homes with a strong emphasis on prevention and health education.4 Foundation endeavors also served the purpose of denazifying and democratizing postwar Germany. Nurses like physicians, midwives, and other health care professionals were in close contact with the population and were seen as important disseminators of a new democratic thinking.5The Heidelberg School of Nursing initially provided only basic training; but in the mid-1950s, it was also a training center for nursing teachers. It was the first institution in the Federal Republic of Germany to offer special training in nursing pedagogy. The teacher-nurses of the school were expected to have completed a further training course in the United States.6 In this way, the Heidelberg School played a central part in the transfer of American nursing concepts to West Germany. Graduates were often called "Hollywood" nurses, "Hollies" for short. Although it is not clear how the term originated, the meaning was that the Hollywood nurses, like actors, only pretended to be nurses and were not "real" German nurses. In the West German nursing landscape, the "American" reform school met a strong resistance. It is a good example of the enormous conflicts that could arise from international transfer of nursing and training concepts.The departments of Nursing Science established at universities and universities of applied sciences since the 1990s have created a specific perspective on the history of the Heidelberg School of Nursing. The resistance to the American reform school has been seen as evidence of the backwardness of German nursing traditions.7 In the eyes of current nurse scientists, the late introduction of higher educational standards in Germany, as compared to the United States, goes back to the strong influence of the Christian view of duty-best exemplified by the motherhouse associations but in the postwar period also held by most nurses in Germany-and the resulting "professional feminine humility. …

Recent advances in sequencing techniques provide means to access direct genetic snapshots from the past with ancient DNA data (aDNA) from diverse periods of human prehistory. Comparing samples taken in the same region but at different time periods may indicate if there is continuity in the peopling history of that area or if a large genetic input, such as an immigration wave, has occurred. Here we propose a new modeling approach for investigating population continuity using aDNA, including two fundamental elements in human evolution that were absent from previous methods: population structure and migration. The method also considers the extensive temporal and geographic heterogeneity commonly found in aDNA datasets. We compare our spatially-explicit approach to the previous non-spatial method and show that it is more conservative and thus suitable for testing population continuity, especially when small, isolated populations, such as prehistoric ones, are considered. Moreover, our approach also allows investigating partial population continuity and we apply it to a real dataset of ancient mitochondrial DNA. We estimate that 91% of the current genetic pool in central Europe entered the area with immigrant Neolithic farmers, but a genetic contribution of local hunter-gatherers as large as 83% cannot be entirely ruled out.

WOS: 000378272400038, PubMed ID: 27274049, Farming and sedentism first appeared in southwestern Asia during the early Holocene and later spread to neighboring regions, including Europe, along multiple dispersal routes. Conspicuous uncertainties remain about the relative roles of migration, cultural diffusion, and admixture with local foragers in the early Neolithization of Europe. Here we present paleogenomic data for five Neolithic individuals from northern Greece and northwestern Turkey spanning the time and region of the earliest spread of farming into Europe. We use a novel approach to recalibrate raw reads and call genotypes from ancient DNA and observe striking genetic similarity both among Aegean early farmers and with those from across Europe. Our study demonstrates a direct genetic link between Mediterranean and Central European early farmers and those of Greece and Anatolia, extending the European Neolithic migratory chain all the way back to southwestern Asia., Marie Curie Initial Training Network (BEAN/Bridging the European and Anatolian Neolithic) [GA 289966]; DFGGerman Research Foundation (DFG) [BU 1403/6-1, BO 4119/1]; Alexander von Humboldt FoundationAlexander von Humboldt Foundation; European Union (EU) SYNTHESYS/Synthesis of Systematic Resources [GA 226506-CP-CSA-INFRA]; VolkswagenstiftungVolkswagen [FKZ: 87161]; Irish Research CouncilIrish Research Council for Science, Engineering and Technology [GOIPG/2013/1219]; EU CodeX Project [295729]; EU Social Fund; Greek national funds research funding program THALES; Greek national funds research funding program ARISTEIA II; Swiss NSFSwiss National Science Foundation (SNSF) [31003A_156853, 31003A_149920]; BBSRCBiotechnology and Biological Sciences Research Council (BBSRC) [BB/L009382/1]; CoMPLEX via EPSRC [EP/F500351/1]; Sir Henry Dale Fellowship - Wellcome Trust [098386/Z/12/Z]; Sir Henry Dale Fellowship - Royal Society [098386/Z/12/Z]; National Institute for Health Research University College London Hospitals Biomedical Research Centre; Wellcome TrustWellcome Trust [100719/Z/12/Z]; University of Mainz; HPC cluster MOGON - DFG [INST 247/602-1 FUGG]; Netherlands Organization for Scientific ResearchNetherlands Organization for Scientific Research (NWO) [380-62-005]; Biotechnology and Biological Sciences Research CouncilBiotechnology and Biological Sciences Research Council (BBSRC) [BB/L009382/1]; Engineering and Physical Sciences Research CouncilEngineering & Physical Sciences Research Council (EPSRC) [1357822], We thank Songul Alpaslan for help with sampling in Barcin and Eleni Stravopodi for help with sampling in Theopetra. Z.H. and R.M. are supported by a Marie Curie Initial Training Network (BEAN/Bridging the European and Anatolian Neolithic, GA 289966) awarded to M.C., S.J.S., D.G.B., M.G.T., and J. Burger. C.P., J. Burger and S.K. received funding from DFG (BU 1403/6-1). C.P. and J. Burger received funding from the Alexander von Humboldt Foundation. C.S. and M.S. were supported by the European Union (EU) SYNTHESYS/Synthesis of Systematic Resources GA 226506-CP-CSA-INFRA, DFG: (BO 4119/1) and Volkswagenstiftung (FKZ: 87161). L.M.C. is funded by the Irish Research Council (GOIPG/2013/1219). A.S. was supported by the EU CodeX Project 295729. K. Kotsakis, S.T., D.U.-K., P.H., and C.P. were cofinanced by the EU Social Fund and Greek national funds research funding program THALES. C.P., M.U., K. Kotsakis, S.T., and D.U.-K. were cofinanced by the EU Social Fund and the Greek national funds research funding program ARISTEIA II. M.C. was supported by Swiss NSF Grant 31003A_156853. A. K. and D.W. were supported by Swiss NSF Grant 31003A_149920. S.L. is supported by the BBSRC (Grant BB/L009382/1). L.v.D. is supported by CoMPLEX via EPSRC (Grant EP/F500351/1). G.H. is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant 098386/Z/12/Z) and by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. M.G.T. and Y.D. are supported by a Wellcome Trust Senior Research Fellowship Grant 100719/Z/12/Z (to M.G.T.). J. Burger is grateful for support by the University of Mainz and the HPC cluster MOGON (funded by DFG; INST 247/602-1 FUGG). F.G. was supported by Grant 380-62-005 of the Netherlands Organization for Scientific Research.

In vertebrates little is known about causes and correlates of differences in individual body condition. This is, however, essential if we are to gain an understanding of environmental influences on wild populations. To track changes in individual physiological state we analysed blood metabolite concentrations in breeding common terns Sterna hirundo. We selected birds to contrast sex, breeding experience, sampling year and nutritional state and collected repeated samples from individuals during incubation. Unlike cholesterol, triglyceride and uric acid levels strongly correlated with nutritional state. While cholesterol levels in males remained stable throughout incubation, comparatively lower levels were measured in females directly after egg-laying. In 2006, only highly experienced females showed increased cholesterol concentrations by mid-incubation, whereas less experienced females maintained reduced levels and were apparently unable to recover. In 2007, all females showed an increase in cholesterol by mid-incubation. Triglyceride levels did not differ between sexes, but concentrations were significantly higher in more experienced birds and were overall higher in 2007 than in 2006. Uric acid concentrations did not differ significantly. The variation in cholesterol and triglyceride levels can be explained by differences in foraging conditions, as food abundance, onset of breeding and mean clutch size indicate 2007 to be the superior year. Thus, environmental conditions and breeding experience play an important role for cholesterol and triglyceride levels as well as the physiological state.

Protestant Deaconess Motherhouses emerged as a German nursing organization in the nineteenth century to be later exported to many other countries including the United States. The motherhouse principle could not be simply transferred without being adapted to the situation prevailing in each of those countries. The essay investigates the conception and transformation of Protestant nursing by comparing a West German and American deaconess motherhouse each in their particular context. It shows that the deaconesses in the United States developed their own, more scientifically oriented understanding of nursing and were therefore more open to the rationalization of nursing than their West German counterpart.

In Lutheran Germany, parish nursing traditionally constituted the deaconesses' principal work. As "Christian mothers of the parish" they were charged with a wide spectrum of tasks, including nursing, social service, and pastoral care. At the center of the Christian understanding of nursing was the idea of nursing body and soul as a unity. This article analyzes the conception and transformation of Protestant parish nursing in the nineteenth and twentieth centuries in Germany and the United States, which developed very differently. In West Germany, parish nursing proved surprisingly resistant to modernization even in the face of upheavals of the 1960s, and in some places this traditional model survived as late as the 1980s and 1990s. In the United States, by contrast, an understanding of nursing rooted in the division of labor between care for body and care for soul had come to prevail by the 1920s and '30s, pushing out the German model of the parish deaconess altogether. When the first German Lutheran deaconess motherhouse was founded in Kaiserswerth near Dusseldorf in 1836, its focus was not on hospital work but on sending nurses to work in parishes. The parish deaconess was regarded as the "crown of the Female Diaconate." 1 As a "Christian mother of the parish," she was charged with a wide spectrum of tasks, including nursing, social service work, and pastoral care. The pastoral care she provided, however, as opposed to the work of the parish pastors, was called "care of the soul." At the center of the Christian understanding of nursing was the idea of nursing body and soul as a unity. 2 Modeled on the Kaiserswerth example, deaconess institutions were founded not only in German-speaking areas but in many other countries. Some of them sprang from the initiative of German motherhouses and some were established by local women who followed the Kaiserswerth model. Founding activities in Scandinavia were particularly successful. In the United States as well, German, Swedish, and Norwegian immigrant communities established deaconess institutions. The focus of this article is on German deaconess establishments in the United States as they compare to such establishments in Germany. These Protestant motherhouses, like the Catholic model they followed, were based on a simple principle of exchange: The sisters were promised training and lifelong care and support with their pledge to service in the sisterhood. Still, the idea of the motherhouse and the role of the deaconess could not be simply transplanted but had to be adapted to the American social context. It is this process of adaptation that makes the deaconess motherhouses an excellent focus for an international comparative history study. 3 Two very different traditions of nursing in Germany and the United States are central in this study. During the nineteenth century in Germany and continuing into the 1960s, the motherhouse system was the dominant organizational form in nursing. Foundationally, nursing in West Germany was based on the Christian model of caring, combining both physical and spiritual care. Later the occupational field was fundamentally restructured: The formerly celibate "labor of love" devoted to the sick became a female profession brought in line with labor law provisions and scientific standards. 4 In the United States, by contrast, a professional strategy emphasizing efficiency, standardization, and scientific management began to characterize the development of nursing as early as the nineteenth century, and deaconess institutions remained marginal. 5 In this article, I investigate the factors responsible for the differences in how well deaconess motherhouses in the two countries were able to establish themselves and take a closer look at one traditional area of nursing that constituted the deaconesses' principal work: parish nursing. I examine two deaconess motherhouses in particular: first, the Henriettenstiftung, which was founded in Hannover, Germany, in 1860 and, alongside parish nursing, was active in a number of other areas of nursing and social work; and second, the German American Lutheran deaconess motherhouse established in Baltimore in 1895, which specialized in parish nursing and teaching deaconesses. …

In West Germany in the early 1950s, it was taken for granted that a "good" nurse would consider her occupation not just a job but a vocation. For her, nursing was not a labor but a service. The large motherhouse sisterhoods of Caritas, the Inner Mission, and the German Red Cross still dominated the nursing vocation in West Germany. When joining a sisterhood, women vowed to subordinate their lives completely to the service of the community and to the service of the sick and needy. In return, the motherhouse provided training and lifelong support. Food and accommodation apart, the motherhouse sisters received only a minimal amount of pocket money. The beginning of the twentieth century saw the founding-as an alternative to the motherhouse system-of so-called free sisterhoods. Their members did not establish a permanent bond with their sisterhood and they did receive a salary for their work.1 Nevertheless, in the early 1950s, the concept of a religious calling still shaped the working and living conditions of these "free" nurses. They lived just as the motherhouse sisters did, in hospital residences. It was understood that nurses would be single and be prepared to work, more often than not, seventy to eighty hours a week, and that, even when working in the public service, their income would fall somewhere very near the bottom of the salary scale. However, in the 1960s, this vocational image changed thoroughly. The traditional ethos of dedicated service became less and less compatible with the lifestyle expectations of a new generation of women; the formerly celibate and self-sacrificial "charity service" (Liebesdienst) was revamped into a modern female occupation that could also be engaged in part-time by married women. In addition, medical progress had profoundly changed the demands made of nursing personnel. It was less and less a "calling for charity."2 Now the demands were for nurses with far more soundly and theoretically based training and qualifications. The present article has a twofold purpose: to present an overview of this process of transformation, and to explore the history of this reform process as it was manifested in everyday life and experience, using a north German motherhouse-the Henriettenstiftung in Hanover-as an example.3 Christian nursing proves particularly interesting when used as a prism through which to examine the modernization process. The pronounced patient orientation of Christian nursing was hardly compatible with the demands made by a modern-day rational and professional value system. Consequently, the ambivalence of the modernization process can clearly be observed.4 The article deals with three aspects of this phenomenon. First, I outline the traditional concept of nursing as a religious calling and analyze its basic tenets. I explore the place in the system of sick care that the sisters occupied, and the way they organized their everyday nursing activities. My focus then shifts to the modernization of nursing in the 1960s. By looking at reforms in training and working hours, I show that modernization meant fragmentation-with far-reaching consequences for the self-concept and everyday practice of nursing. Finally, I locate this process of transformation within the general history of society and medicine. The article is based on contemporary publications and health care periodicals, as well as interviews with the deaconesses of the Henriettenstiftung. I have also analyzed the comprehensive archives of the Henriettenstiftung, which contain the personnel files of about 900 sisters belonging to the motherhouse in the post-World War II period. Through these means, the everyday life as well as the self-image of the sisters and their perspectives on modernization can be clearly traced. Nursing as a Religious Calling In the course of the nineteenth century, the motherhouse system developed into the dominant form of nursing organization in Germany, remaining relatively unchanged well into the second half of the twentieth century. …