RESUMO
Yersinia pestis has been infecting humans since the Late Neolithic (LN). Whether those early infections were isolated zoonoses or initiators of a pandemic remains unclear. We report Y. pestis infections in two individuals (of 133) from the LN necropolis at Warburg (Germany, 5300-4900 cal BP). Our analyses show that the two genomes belong to distinct strains and reflect independent infection events. All LN genomes known today (n = 4) are basal in the phylogeny and represent separate lineages that probably originated in different animal hosts. In the LN, an opening of the landscape resulted in the introduction of new rodent species, which may have acted as Y. pestis reservoirs. Coincidentally, the number of dogs increased, possibly leading to Y. pestis infections in canines. Indeed, we detect Y. pestis in an LN dog. Collectively, our data suggest that Y. pestis frequently entered human settlements at the time without causing significant outbreaks.
Assuntos
Doenças do Cão , Filogenia , Peste , Yersinia pestis , Animais , Yersinia pestis/genética , Yersinia pestis/isolamento & purificação , Cães/microbiologia , Peste/microbiologia , Peste/epidemiologia , Peste/história , Peste/transmissão , Humanos , Doenças do Cão/microbiologia , Alemanha/epidemiologia , Genoma Bacteriano , História AntigaRESUMO
The Wartberg culture (WBC, 3500-2800 BCE) dates to the Late Neolithic period, a time of important demographic and cultural transformations in western Europe. We performed genome-wide analyses of 42 individuals who were interred in a WBC collective burial in Niedertiefenbach, Germany (3300-3200 cal. BCE). The results showed that the farming population of Niedertiefenbach carried a surprisingly large hunter-gatherer ancestry component (34-58%). This component was most likely introduced during the cultural transformation that led to the WBC. In addition, the Niedertiefenbach individuals exhibited a distinct human leukocyte antigen gene pool, possibly reflecting an immune response that was geared towards detecting viral infections.
Assuntos
Agricultura , Comportamento Alimentar/fisiologia , Antígenos HLA/genética , Comportamento Predatório/fisiologia , Animais , Arqueologia , DNA Antigo/análise , Europa (Continente) , Evolução Molecular , Variação Genética , Genética Populacional , Genoma Humano , Estudo de Associação Genômica Ampla , Alemanha , História Antiga , Migração Humana , Humanos , Polimorfismo de Nucleotídeo Único , Grupos Raciais/genética , Características de ResidênciaRESUMO
OBJECTIVE: Metabolic exhaustion in ischemic tissue is the basis for a detrimental cascade of cell damage. In the acute stage of subarachnoid hemorrhage (SAH), a sequence of global and focal ischemia occurs, threatening brain tissue to undergo ischemic damage. This study was conducted to investigate whether early therapy with moderate hypothermia can offer neuroprotection after experimental SAH. METHODS: Twenty male Sprague-Dawley rats were subjected to SAH and treated by active cooling (34°C) or served as controls by continuous maintenance of normothermia (37.0°C). Mean arterial blood pressure, intracranial pressure, and local cerebral blood flow over both hemispheres were continuously measured. Neurologic assessment was performed 24 hours later. Hippocampal damage was assessed by hematoxylin-eosin and caspase-3 staining. RESULTS: By a slight increase of mean arterial blood pressure in the cooling phase and a significant reduction of intracranial pressure, hypothermia improved cerebral perfusion pressure in the first 60 minutes after SAH. Accordingly, a trend to increased cerebral blood flow was observed during this period. The rate of injured neurons was significantly reduced in hypothermia-treated animals compared with normothermic controls. CONCLUSIONS: The results of this series cannot finally answer whether this form of treatment permanently attenuates or only delays ischemic damage. In the latter case, slowing down metabolic exhaustion by hypothermia may still be a valuable treatment during this state of ischemic brain damage and prolong the therapeutic window for possible causal treatments of the acute perfusion deficit. Therefore, it may be useful as a first-tier therapy in suspected SAH.
Assuntos
Lesões Encefálicas/patologia , Lesões Encefálicas/prevenção & controle , Hipotermia Induzida/métodos , Doenças do Sistema Nervoso/patologia , Doenças do Sistema Nervoso/prevenção & controle , Hemorragia Subaracnóidea/patologia , Animais , Lesões Encefálicas/etiologia , Modelos Animais de Doenças , Fluxometria por Laser-Doppler/métodos , Masculino , Doenças do Sistema Nervoso/etiologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Hemorragia Subaracnóidea/complicações , Fatores de TempoRESUMO
OBJECTIVE: Early cytotoxic brain edema may be a decisive factor that maintains cerebral malperfusion after subarachnoid hemorrhage (SAH). In addition, endothelial cell swelling may be an independent factor restricting cerebral blood flow (CBF) in a very early stage after SAH. Immediate and aggressive treatment may be able to restore CBF in this critical period. METHODS: Male Sprague-Dawley rats were subjected to SAH by the endovascular filament model and treated by a bolus of hyperoncotic-hypertonic hydroxyethyl starch (4 mL/kg body weight) immediately after vessel perforation and 150 minutes later (n = 12) or by the same amount of normal saline (n = 9). Mean arterial blood pressure, intracranial pressure, and local CBF over both hemispheres were continuously measured by laser-Doppler flowmetry. Neurologic assessment was performed 24 hours later. Hippocampal damage was assessed by hematoxylin-eosin and Caspase-3 staining. RESULTS: Arterial blood gases and mean arterial blood pressure were not significantly different between the 2 groups. Intracranial pressure was significantly reduced in the treatment group (P < 0.05). Local CBF was significantly improved in the treatment group over both hemispheres (P < 0.05; 180 minutes after treatment, P < 0.01). There was a trend to better neurologic performance in the treatment group. The rate of injured neurons was significantly reduced in animals of the treatment group compared with controls (P < 0.01). The number of Caspase-3-positive neurons in the hippocampal CA1 field was not reduced. CONCLUSIONS: In this study, the effects of very early and repeated treatment with a high-dose hyperoncotic-hypertonic hydroxyethyl starch were investigated. The results of this series show that this therapy can be highly effective to improve CBF and attenuate hippocampal cell damage in the early stage of SAH. Whether delayed cell death could be treated by longer therapy cannot be answered by this study. Because no differential diagnosis of the clinical suspicion of SAH prohibits the administration of hypertonic-hyperoncotic solutions, it may be useful as a first-tier preclinical therapy in suspected SAH and could even be used by emergency rescue services before the patient is admitted to a hospital.
Assuntos
Circulação Cerebrovascular/efeitos dos fármacos , Pressão Intracraniana/efeitos dos fármacos , Amido/farmacologia , Hemorragia Subaracnóidea/tratamento farmacológico , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Circulação Cerebrovascular/fisiologia , Modelos Animais de Doenças , Pressão Intracraniana/fisiologia , Masculino , Ratos Sprague-Dawley , Amido/administração & dosagem , Fatores de Tempo , Resultado do Tratamento , Vasoespasmo Intracraniano/tratamento farmacológico , Vasoespasmo Intracraniano/fisiopatologiaRESUMO
The hepatitis B virus (HBV) is one of the most widespread human pathogens known today, yet its origin and evolutionary history are still unclear and controversial. Here, we report the analysis of three ancient HBV genomes recovered from human skeletons found at three different archaeological sites in Germany. We reconstructed two Neolithic and one medieval HBV genome by de novo assembly from shotgun DNA sequencing data. Additionally, we observed HBV-specific peptides using paleo-proteomics. Our results demonstrated that HBV has circulated in the European population for at least 7000 years. The Neolithic HBV genomes show a high genomic similarity to each other. In a phylogenetic network, they do not group with any human-associated HBV genome and are most closely related to those infecting African non-human primates. The ancient viruses appear to represent distinct lineages that have no close relatives today and possibly went extinct. Our results reveal the great potential of ancient DNA from human skeletons in order to study the long-time evolution of blood borne viruses.