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Extensive spatial and temporal distribution of high-quality data are essential for understanding regional and global behaviors of the geomagnetic field. We carried out chronological and archaeomagnetic studies at the Angkor-era iron-smelting site of Tonle Bak in Cambodia in Southeast Asia, an area with no data available to date. We recovered high-fidelity full-vector geomagnetic information from the 11th to 14th century for this region, which fill gaps in the global distribution of data and will significantly improve the global models. These results reveal a sharp directional change of the geomagnetic field between 1200 and 1300 CE, accompanied by an intensity dip between 1100 and 1300 CE. The fast geomagnetic variation recorded by our data provides evidence for the possible existence of low-latitude flux expulsion. Related discussions in this paper will inspire a new focus on detailed geomagnetic research in low-latitude areas around the equator, and exploration of related dynamic processes.
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Methane (CH4) is a powerful greenhouse gas and plays a key part in global atmospheric chemistry. Natural geological emissions (fossil methane vented naturally from marine and terrestrial seeps and mud volcanoes) are thought to contribute around 52 teragrams of methane per year to the global methane source, about 10 per cent of the total, but both bottom-up methods (measuring emissions) and top-down approaches (measuring atmospheric mole fractions and isotopes) for constraining these geological emissions have been associated with large uncertainties. Here we use ice core measurements to quantify the absolute amount of radiocarbon-containing methane (14CH4) in the past atmosphere and show that geological methane emissions were no higher than 15.4 teragrams per year (95 per cent confidence), averaged over the abrupt warming event that occurred between the Younger Dryas and Preboreal intervals, approximately 11,600 years ago. Assuming that past geological methane emissions were no lower than today, our results indicate that current estimates of today's natural geological methane emissions (about 52 teragrams per year) are too high and, by extension, that current estimates of anthropogenic fossil methane emissions are too low. Our results also improve on and confirm earlier findings that the rapid increase of about 50 per cent in mole fraction of atmospheric methane at the Younger Dryas-Preboreal event was driven by contemporaneous methane from sources such as wetlands; our findings constrain the contribution from old carbon reservoirs (marine methane hydrates, permafrost and methane trapped under ice) to 19 per cent or less (95 per cent confidence). To the extent that the characteristics of the most recent deglaciation and the Younger Dryas-Preboreal warming are comparable to those of the current anthropogenic warming, our measurements suggest that large future atmospheric releases of methane from old carbon sources are unlikely to occur.
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Atmosfera/química , Aquecimento Global/história , Metano/análise , Metano/história , Carbono/análise , Carbono/química , Combustíveis Fósseis/análise , História Antiga , Gelo/análise , Metano/química , Datação Radiométrica , Áreas AlagadasRESUMO
The time of arrival of people in Australia is an unresolved question. It is relevant to debates about when modern humans first dispersed out of Africa and when their descendants incorporated genetic material from Neanderthals, Denisovans and possibly other hominins. Humans have also been implicated in the extinction of Australia's megafauna. Here we report the results of new excavations conducted at Madjedbebe, a rock shelter in northern Australia. Artefacts in primary depositional context are concentrated in three dense bands, with the stratigraphic integrity of the deposit demonstrated by artefact refits and by optical dating and other analyses of the sediments. Human occupation began around 65,000 years ago, with a distinctive stone tool assemblage including grinding stones, ground ochres, reflective additives and ground-edge hatchet heads. This evidence sets a new minimum age for the arrival of humans in Australia, the dispersal of modern humans out of Africa, and the subsequent interactions of modern humans with Neanderthals and Denisovans.
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Migração Humana/história , África/etnologia , Animais , Austrália , Dieta/história , Fósseis , Sedimentos Geológicos/análise , História Antiga , Humanos , Homem de NeandertalRESUMO
Global warming causes the poleward shift of the trailing edges of marine ectotherm species distributions. In the semi-enclosed Mediterranean Sea, continental masses and oceanographic barriers do not allow natural connectivity with thermophilic species pools: as trailing edges retreat, a net diversity loss occurs. We quantify this loss on the Israeli shelf, among the warmest areas in the Mediterranean, by comparing current native molluscan richness with the historical one obtained from surficial death assemblages. We recorded only 12% and 5% of historically present native species on shallow subtidal soft and hard substrates, respectively. This is the largest climate-driven regional-scale diversity loss in the oceans documented to date. By contrast, assemblages in the intertidal, more tolerant to climatic extremes, and in the cooler mesophotic zone show approximately 50% of the historical native richness. Importantly, approximately 60% of the recorded shallow subtidal native species do not reach reproductive size, making the shallow shelf a demographic sink. We predict that, as climate warms, this native biodiversity collapse will intensify and expand geographically, counteracted only by Indo-Pacific species entering from the Suez Canal. These assemblages, shaped by climate warming and biological invasions, give rise to a 'novel ecosystem' whose restoration to historical baselines is not achievable.
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Biodiversidade , Ecossistema , Mar MediterrâneoRESUMO
Gene function studies benefit from the availability of mutants. In plants, Agrobacterium-mediated genetic transformation is widely used to create mutants. These mutants, also called transformants, contain one or several transfer-DNA (T-DNA) copies in the host genome. Quantifying the copy number of T-DNA in transformants is beneficial to assess the number of mutated genes. Here, we developed a competitive polymerase chain reaction (PCR)-based method to detect a single copy of a T-DNA insertion in transformants. The competitor line BHK- -1 that contains a single copy of competitor BHK- (BHK, Basta, Hygromycin, Kanamycin-resistant genes) was crossed with test transformants and the genomic DNA of F1 plants was subjected to competitive PCR. By analyzing the gray ratio between two PCR products, we were able to determine whether or not the test transformants contained a single copy of T-DNA insertion. We also generated the control lines BHK±1:1 and BHK±2:1 , which contain the target (BHK+ ) and competitor (BHK- ) in a ratio of 1:1 and 2:1, respectively. The ratios of their PCR products are useful references for quantitative analysis. Overall, this method is reliable and simple in experimental manipulations and can be used as a substitute for Southern-blot analysis to identify a single copy of T-DNA insertion in transformants.
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DNA , DNA Bacteriano/genética , Reação em Cadeia da Polimerase , Transformação GenéticaRESUMO
Intracranial hemorrhage (ICH) is a devastating complication of immune thrombocytopenia (ITP). However, information on ICH in ITP patients under the age of 60 years is limited, and no predictive tools are available in clinical practice. A total of 93 adult patients with ITP who developed ICH before 60 years of age were retrospectively identified from 2005 to 2019 by 27 centers in China. For each case, 2 controls matched by the time of ITP diagnosis and the duration of ITP were provided by the same center. Multivariate analysis identified head trauma (OR = 3.216, 95%CI 1.296-7.979, P =.012), a platelet count ≤ 15,000/µL at the time of ITP diagnosis (OR = 1.679, 95%CI 1.044-2.698, P =.032) and severe/life-threatening bleeding (severe bleeding vs. mild bleeding, OR = 1.910, 95%CI 1.088-3.353, P =.024; life-threatening bleeding vs. mild bleeding, OR = 2.620, 95%CI 1.360-5.051, P =.004) as independent risk factors for ICH. Intraparenchymal hemorrhage (OR = 5.191, 95%CI 1.717-15.692, P =.004) and a history of severe bleeding (OR = 4.322, 95%CI 1.532-12.198, P =.006) were associated with the 30-day outcome of ICH. These findings may facilitate ICH risk stratification and outcome prediction in patients with ITP.
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Hemorragias Intracranianas/etiologia , Púrpura Trombocitopênica Idiopática/complicações , Feminino , Humanos , Hemorragias Intracranianas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Resultado do TratamentoRESUMO
Forward genetic analysis, widely used to find new gene functions, benefits from the availability of mutants. At present, based on Agrobacterium-mediated plant transformation technology, many transfer (T)-DNA transformants have been created. However, cloning their T-DNA insertion sites, which enables identification of the mutated genes, is still challenging. In this study, we improved adapter ligation-mediated polymerase chain reaction (A-PCR), which mainly utilizes the Thermal Asymmetric interlaced reaction and Degenerate sequence-recognizing restriction Endonucleases (TADE). Using the new method TADE-mediated A-PCR (TADEA-PCR), we successfully cloned 22 of all the 24 junction sites in 10 Arabidopsis thaliana L. transformants that contained 12 T-DNA insertions in total, giving a success rate of 91.7%. In most cases, the two junction sites resulting from a single T-DNA insertion were simultaneously cloned. In addition, TADEA-PCR was able to clone more than two junction sites present in one transformant containing several T-DNA insertions. Overall, TADEA-PCR is a powerful technique for cloning T-DNA insertion sites.
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DNA Bacteriano/genética , Reação em Cadeia da Polimerase/métodos , Mutação , Análise de Sequência de DNARESUMO
Subsoils contain large amounts of organic carbon which is generally believed to be highly stable when compared with surface soils. We investigated subsurface organic carbon storage and dynamics by analysing organic carbon concentrations, fractions and isotopic values in 78 samples from 12 sites under different land-uses and climates in eastern Australia. Despite radiocarbon ages of several millennia in subsoils, contrasting native systems with agriculturally managed systems revealed that subsurface organic carbon is reactive on decadal timeframes to land-use change, which leads to large losses of young carbon down the entire soil profile. Our results indicate that organic carbon storage in soils is input driven down the whole profile, challenging the concept of subsoils as a repository of stable organic carbon.
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Agricultura , Sequestro de Carbono , Solo/química , Austrália , CarbonoRESUMO
OBJECTIVE: The methylation of paired box gene 1 (PAX1) has a great influence on the process of cervical lesion. However, available evidence for the association between PAX1 methylation and cervical intraepithelial neoplasia (CIN) are inconsistent. Here, we systematically reviewed and analyzed PAX1 methylation in progress of CIN. METHODS: Two investigators independently searched eligible studies of PAX1 methylation and CIN that were published in PubMed, Cochrane Library, EMBASE, and Web of Science databases until November 30, 2016. We extracted clinicopathologic features of CIN and cervical cancel relevant to PAX1 methylation. Odds ratios (ORs) with their 95% confidence intervals (CIs) were used to assess the association between PAX1 methylation and progression of patients with CIN. RESULTS: Seven studies composed of 1055 patients with various stages of CIN and cervical cancel were eventually included. The results revealed that PAX1 methylation was associated with transition of CIN I to CIN II/III (OR, 0.09; 95% CI, 0.04-0.19) and CIN II/III to cervical cancer (OR, 0.16; 95% CI, 0.05-0.46), and similar results were produced in sensitivity analysis. Also, we found that the OR value was associated with average age and number of patients, publication year, and study location of included articles. CONCLUSIONS: PAX1 gene methylation was associated with the transition of CIN I to CIN II/III and CIN II/III to cervical cancer, so that it could be an auxiliary biomarker to estimate the risk of CIN progress. Moreover, PAX1 may help to determine appropriate reexaminations and treatment for patients with various stages of CIN.
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Biomarcadores Tumorais/genética , Metilação de DNA , Fatores de Transcrição Box Pareados/genética , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/genética , Adulto , Progressão da Doença , Feminino , Humanos , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Displasia do Colo do Útero/metabolismo , Displasia do Colo do Útero/patologiaRESUMO
The mortality of conservative treatment and the risk resulting from operation for elderly patients with femoral intertrochanteric fractures are high. Safety in the perioperative period and quicker recovery should be placed at the top priority for elderly patients with hip fractures. We reported a case of 109-year-old female patient with intertrochanteric fracture who has undergone the hemiarthroplasty in our center recently. With sciatic nerve and lateral cutaneous nerve block anesthesia, she was offered the artificial femoral head replacement in the lumbar plexus block after sufficient preoperative preparation. The surgery went well with minimally invasive cut, and the patient's recovery was satisfactory.
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Hemiartroplastia/métodos , Fraturas do Quadril/cirurgia , Idoso de 80 Anos ou mais , Feminino , Humanos , Bloqueio NervosoRESUMO
In this study, we present a comprehensive atmospheric radiocarbon (14C) record spanning from 1940 to 2016, derived from 77 single tree rings of Cedrela odorata located in the Eastern Amazon Basin (EAB). This record, comprising 175 high-precision 14C measurements obtained through accelerator mass spectrometry (AMS), offers a detailed chronology of post-1950 CE (Common Era) 14C fluctuations in the Tropical Low-Pressure Belt (TLPB). To ensure accuracy and reliability, we included 14C-AMS results from intra-annual successive cuts of the tree rings associated to the calendar years 1962 and 1963 and conducted interlaboratory comparisons. In addition, 14C concentrations in 1962 and 1963 single-year cuts also allowed to verify tissue growth seasonality. The strategic location of the tree, just above the Amazon River and estuary areas, prevented the influence of local fossil-CO2 emissions from mining and trade activities in the Central Amazon Basin on the 14C record. Our findings reveal a notable increase in 14C from land-respired CO2 starting in the 1970s, a decade earlier than previously predicted, followed by a slight decrease after 2000, signaling a transition towards the fossil fuel era. This shift is likely attributed to changes in reservoir sources or global atmospheric dynamics. The EAB 14C record, when compared with a shorter record from Muna Island, Indonesia, highlights regional differences and contributes to a more nuanced understanding of global 14C variations at low latitudes. This study not only fills critical spatial gaps in existing 14C compilations but also aids in refining the demarcation of 14C variations over South America. The extended tree-ring 14C record from the EAB is pivotal for reevaluating global patterns, particularly in the context of the current global carbon budget, and underscores the importance of tropical regions in understanding carbon-climate feedbacks.
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Dióxido de Carbono , Clima , Reprodutibilidade dos Testes , Carbono , América do SulRESUMO
Mineral aerosols form a key component of Earth's dynamic biogeochemical systems, yet their composition and mass are variable in time. We reconstruct patterns in mineral aerosol flux from East Asia, the second largest global dust source, in a peat mire in northern Japan. Using geochemical fingerprinting, we show for the past ~3600 years that high but variable tephra flux dominated regional aerosol loads. A human signal was discernible as elevated pollutant metals, along with East Asian mainland dust, identifiable by its geochemical signature. After ~700 years before the present, dust flux increased as the westerly jet intensified and moved south, the summer monsoon strength reduced, and agriculture expanded. From the 20th century, dust flux increased by two times. Attributable largely to human activity, this demarks a major change in aerosol export to the northwestern Pacific with accompanying increases in fluxes for key micronutrients and increased pollution flux by 16 times.
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Aerossóis , Poeira , Material Particulado , Erupções Vulcânicas , Humanos , Poeira/análise , Erupções Vulcânicas/história , Erupções Vulcânicas/análise , Aerossóis/análise , Material Particulado/análise , Atmosfera/química , História Antiga , Poluentes Atmosféricos/análise , Oceano Pacífico , Monitoramento Ambiental/métodosRESUMO
OBJECTIVE: To explore the relationship between the dendritic cell (DC) subsets and abnormal expression of transcription factors Gata-3 and T-bet in patients with immune thrombocytopenia (ITP). METHODS: The plasmacytoid DC (pDC) and myeloid DC (mDC) of 33 ITP (16 untreated, 17 remitted) patients and 12 healthy controls were analyzed by flow cytometry (FCM) . The expressions of Gata-3 mRNA and T-bet mRNA in peripheral blood mononuclear cell (PBMNC) were detected by reverse transcription-polymerase chain reaction (RT-PCR) .The levels of interleukin-4 (IL-4) and interferon-gamma (IFN-γ) were measured by FCM in 33 ITP patients and 12 healthy controls. RESULTS: The percentage of pDC in PBMNC was 0.49% ± 0.18% in untreated and it was higher than that in remitted ITP patients (0.27% ± 0.17%) and in controls (0.32% ± 0.13%) (both P < 0.05). The percentage of mDC in PBMNC was 0.23% ± 0.17% in untreated, which was lower than that in remitted ITP patients (0.33% ± 0.18)% and in controls (0.31% ± 0.11%), but no statistic difference in mDC expression existed among 3 groups (P > 0.05). pDC/mDC ratios was (3.15 ± 2.01) in untreated ITP patients and it was higher than that in remitted ITP patients (0.81 ± 0.32) and in controls (1.07 ± 0.44) (both P < 0.05). The relative mRNA expression levels of Gata-3 were 2775 ± 489, 1357 ± 307 and 652 ± 165 respectively. And the expression of Gata-3mRNA in untreated group was higher than that in remission group or healthy controls (both P < 0.05). The relative mRNA expression levels of T-bet were 782 ± 394, 583 ± 176 and 576 ± 120. No statistic difference in T-bet expression existed among 3 groups (P > 0.05). Gata-3mRNA/T-bet mRNA ratio was (4.13 ± 1.69 ) in untreated group and it was higher than that of remission group (2.45 ± 0.69) or controls (1.15 ± 0.27) (both P < 0.05). The level of IL-4 in the untreated group was 9.14% ± 4.34% and it was higher than that of remission group (4.78% ± 1.69%) or controls (4.86% ± 1.41%). The level of IFN-γ in the untreated group was lower than that of controls (P < 0.05). Significant positive correlations existed between Gata-3 and pDC/mDC ratio (r = 0.585, P < 0.01). Significant positive correlations existed between Gata-3 and IL-4 ( r = 0.463, P < 0.05). CONCLUSION: The mechanism of ITP may be due to a disorder of DC subsets and a high expression of Gata-3.
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Células Dendríticas/metabolismo , Fator de Transcrição GATA3/metabolismo , Proteínas com Domínio T/metabolismo , Trombocitopenia/metabolismo , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Feminino , Humanos , Interferon gama/sangue , Interleucina-4/sangue , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Trombocitopenia/etiologia , Trombocitopenia/imunologia , Adulto JovemRESUMO
OBJECTIVE: To explore the inhibitory effects of tacrolimus (FK506) on effector T cells in vitro and examine the relationship between effector T cells and clinical features in patients with severe aplastic anemia (SAA) to elucidate its immune mechanism. METHODS: The CD8(+) HLA-DR(+) cells, sorted by immunomagnetic separation from bone marrow mononuclear cells (BMMNC) of 16 SAA patients, were cultured in different concentrations of interleukin-2 (IL-2) alone or with FK506 for 72 hours. The proliferation effect was measured with methyl thiazolyl tetrazolium (MTT) method. The T lymphocytes were sorted from the SAA patients by lymphocyte separation medium and cultured alone or with IL-2 or with FK506 or FK506 plus cyclosporin A (CsA) for 18 hours. The expression of tumor necrosis factor-ß (TNF-ß) in CD8(+) HLA-DR(+) T cells was analyzed by flow cytometry. The relationship between the expression of TNF-ß and the clinical data, including percentages of reticulocyte and lymphocytes in peripheral blood cell count and ratio of CD4(+) T cells and CD8(+)T cells, was also analyzed. RESULTS: At the concentration of IL-2 greater than or equal to 20 U/ml, the cell proliferation (A values, 0.538 ± 0.142) were significantly higher than that in the blank culture hole (0.505 ± 0.153) (P < 0.05). The A values significantly decreased (0.386 ± 0.124) after the addition of FK506 (P < 0.05). Compared with control group, the expression of TNF-ß was significantly higher in IL-2 group (73.36% ± 16.73% vs 66.61% ± 16.20%, P < 0.05), significantly lower in FK506 and FK506 plus CsA groups (P < 0.05). No significant differences existed between the FK506 and FK506 plus CsA groups (47.78% ± 20.09% and 42.23% ± 21.35%, P > 0.05). The expression of TNF-ß in SAA was negatively correlated with the percentage of reticulocyte and the ratio of CD4(+) T cell and CD8(+) T cell, positively correlated with the percentage of lymphocyte in peripheral blood count (r = -0.86, -0.90, 0.77, all P < 0.05). CONCLUSIONS: IL-2 can enhance the proliferation and expression of TNF-ß of CD8(+)HLA-DR(+)T cells from SAA patients. Such an effect is inhibited by FK506. And FK506 and FK506 plus CsA have similar effects.
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Anemia Aplástica/patologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Interleucina-2/farmacologia , Tacrolimo/farmacologia , Adulto , Idoso , Anemia Aplástica/imunologia , Relação CD4-CD8 , Linfócitos T CD8-Positivos/imunologia , Proliferação de Células , Células Cultivadas , Ciclosporina/farmacologia , Feminino , Antígenos HLA-DR , Humanos , Linfotoxina-alfa/metabolismo , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To explore the changes in telomere length and gene expression of complex shelterin (composed of 6 core components: TRF1, TRF2, POT1, TIN2, TPP1 and RAP1) in severe aplastic anemia (SAA). METHODS: Bone marrow samples were obtained from 20 SAA patients and 10 normal controls. CD3(+)T cells were sorted by immunomagnetic separation. Telomere length was tested by Southern blot and the gene expressions of TRF1, TRF2, POT1, TIN2, TPP1 and RAP1 were detected by reverse transcription-PCR(RT-PCR). RESULTS: Telomeres of CD3(+)T cells were found significantly shorter in SAA untreated ((4.4 ± 1.1) kb, n = 9) and recovering groups((5.8 ± 1.0) kb, n = 11) than control group ((9.2 ± 3.3) kb, P < 0.05). Telomere length of CD3(+)T cells shortened with TH/S decreasing (r = 0.564, P = 0.029). The mRNA expression of POT1 decreased in untreated SAA patients (0.16(0.02-0.29)) and over-expressed in recovering patients (1.17(0.82-1.86), P < 0.05). The mRNA expression of RAP1 was significantly higher in untreated patients (4.14 (1.93-6.92)) than that in recovering group (0.87 (0.30-1.73) ) and controls (0.62 (0.45-4.07) , both P < 0.05). CONCLUSION: Changes in telomere length and shelterin gene expression occur in CD3(+)T cells of SAA patients and may be correlated with disease severity.
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Anemia Aplástica/metabolismo , Linfócitos T/metabolismo , Proteínas de Ligação a Telômeros/metabolismo , Telômero/metabolismo , Adolescente , Adulto , Idoso , Anemia Aplástica/genética , Complexo CD3/metabolismo , Estudos de Casos e Controles , Criança , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Complexo Shelterina , Proteínas de Ligação a Telômeros/genética , Adulto JovemRESUMO
Human responses to climate change have long been at the heart of discussions of past economic, social, and political change in the Nile Valley of northeastern Africa. Following the arrival of Neolithic groups in the 6th millennium BCE, the Northern Dongola Reach of Upper Nubia witnessed a cultural florescence manifested through elaborate funerary traditions. However, despite the wealth of archaeological data available from funerary contexts, including evidence for domesticated animals and plants as grave goods, the paucity of stratified habitation contexts hinders interpretation of local subsistence trajectories. While it is recognised archaeologically that, against the backdrop of increasing environmental deterioration, the importance of agriculture based on Southwest Asian winter cereals increased throughout the Kerma period (2500-1450 BCE), the contribution of domesticated cereals to earlier Neolithic herding economies remains unclear. This paper presents direct dietary data from a total of 55 Middle Neolithic and Kerma period individuals from Kadruka 21 and Kadruka 1. Microbotanical data obtained from human dental calculus and grave sediments are integrated with human and faunal stable isotopes to explore changes in dietary breadth over time. The combined results demonstrate the consumption of wild plant species, including C4 wetland adapted grasses, by Middle Neolithic individuals at Kadruka 1. Despite existing evidence for domesticated barley in associated graves, the results obtained in this study provide no clear evidence for the routine consumption of domesticated cereals by Middle Neolithic individuals. Rather, direct microparticle evidence for the consumption of Triticeae cereals is only associated with a single Kerma period individual and corresponds with an isotopic shift indicating a greater contribution of C3-derived resources to diet. These results provide evidence for Neolithic dietary flexibility in Upper Nubia through the persistence of foraging activities and support existing evidence linking increased agricultural reliance to the development of the Kerma culture.
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Animais Domésticos , Mudança Climática , Humanos , Animais , História Antiga , Agricultura , Isótopos , Grão Comestível , Arqueologia , Dieta , PoaceaeRESUMO
The ancient southern Levantine city of Gezer is well-known from Egyptian, Biblical and Assyrian sources, associated with power struggles, conquests, and intriguing tales involving figures such as Milkilu and Amenhotep III, Merneptah, the Philistines, Solomon and his unidentified pharaonic father-in-law, and Shishak / Sheshonq I. Since the identity of Gezer with "Tell Jezer" is quite literally 'set in stone' by some dozen boundary inscriptions, along with impressive Bronze and Iron Age remains, research at this site provides a unique opportunity to compare text and archaeology, as well as bring to light the undocumented everyday lives of the city's inhabitants. In this endeavour, independent scientific dating is crucial for anchoring the remains chronologically. This paper presents the first substantial radiocarbon dataset and Bayesian chronological analysis for Gezer spanning the last part of the Late Bronze Age (LBA; LB IIB) through Iron Age II. The dataset derives from an essentially continuous stratigraphic sequence exposed in recent years by the Tandy expedition along the central-southern edge of the site. The results allow us for the first time to independently determine the site chronology, test the viability (from a chronological perspective) of proposed historical correlations, and contribute to debates on Philistine and Iron Age chronology.
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Arqueologia , Bíblia , Arqueologia/métodos , Teorema de Bayes , Tempo , Datação Radiométrica/métodosRESUMO
OBJECTIVE: To assess the efficacy and safety of monoclonal antibody rituximab combined with cyclophosphamide (CTX) in the treatment of refractory and recurrent autoimmune hemolytic anemia. METHODS: Seven cases with refractory and recurrent autoimmune hemolytic anemia (including 1 case of Evans syndrome) were recruited during January, 2007 to December, 2010. Treatment regimens were as follows: rituximab: 375 mg/m², 1 time/week, 2-6 courses; CTX:1 g, 1/10 d, 2-7 courses; combined with intravenous immunoglobulin (IVIG) 5 g, 1 time/week, given 1 day after rituximab administration. The efficacy and safety of this regimen were assessed during follow-up. RESULTS: All the patients showed good responses (7/7). Six patients achieved complete remission (6/7) and one achieved partial remission (1/7). Average follow-up time for the patients was 27 months. All patients remained in remission during the 12-month follow-up visits. Two patients showed elevated indirect bilirubin and increased reticulocyte counts within 24 months. One patient achieved complete remission after additional rituximab therapy, and another patient remained partial remission after cyclosporine therapy. At the time of 36-month follow-up visit, the patient relapsed and was retreated with 3 courses of rituximab combined with CTX and eventually achieved partial remission. All patients tolerated the treatment well with few mild side effects. CONCLUSIONS: Rituximab combined with CTX is effective and relatively safe in patients with refractory and recurrent autoimmune hemolytic anemia. Additional treatment to relapse patients about 12 - 24 months after drug withdrawal continues to be effective.
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Anemia Hemolítica Autoimune/tratamento farmacológico , Anticorpos Monoclonais Murinos/uso terapêutico , Ciclofosfamida/uso terapêutico , Adolescente , Adulto , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the expression of TET2 and DLK1 mRNA in bone marrow CD(3)(+) T cells of patients with myelodysplastic syndrome (MDS) and their clinical significance and to explore the potential mechanism of abnormal cell-mediated immunity. METHODS: CD(3)(+) T cells were sorted by magnetic activated cell-sorting system. The expressions of TET2 and DLK1 mRNA in bone marrow CD(3)(+) T cells from 26 MDS patients and 16 healthy controls were detected by fluorescence quantitative PCR. RESULTS: The expression of TET2 mRNA in CD(3)(+) T cells was down-regulated in the MDS patients by (0.16 ± 0.15) fold compared with the controls (P < 0.05). The expression of TET2 mRNA in CD(3)(+) T cells of MDS patients was positively correlated with serum complement C(3) (r = 0.404, P < 0.05). The expression of DLK1 mRNA in CD(3)(+) T cells was up-regulated in the MDS patients by (1.61 ± 0.88) folds compared with the controls (P < 0.05). Grouped by the chromosomes, the patients with chromosome abnormalities presented significantly higher DLK1 mRNA level than those with normal chromosomes [(1.45 ± 0.44) folds, P < 0.05]. The expression of DLK1 mRNA in CD(3)(+) T cells of MDS patients was positively correlated with the proportion of bone marrow blasts (r = 0.343, P < 0.05). CONCLUSIONS: The mRNA expression of TET2 in CD(3)(+) T cells of MDS patients was decreased while the mRNA expression of DLK1 was increased, which might decline the immune surveillance function. The findings would be useful for exploring the mechanism of immune tolerance.