Proportion of fetal hemoglobin synthesis decreases during erythroid cell maturation.

Peripheral blood mononuclear cells from pregnant and postpartum women were cultured in vitro with erythropoietin. Burst-forming unit (BFU-E)-derived erythroid colonies composed of immature erythroblasts with low hemoglobin contents were observed by day 8 of culture. By day 12 of culture, numerous BFU-E-derived erythroid colonies with high hemoglobin contents were present. The gamma/(gamma + beta) globin synthetic ratio was approximately 12% in the early cultures and 6% in the late cultures, indicating that the proportion of fetal hemoglobin synthesis decreases during erythroid cell maturation. These studies also reveal that the capacity fof fetal hemoglobin production by peripheral blood BFU-E in vitro is not altered during pregnancy.     

Human embryonic zeta-globin chain expression in deletional alpha-thalassemias.

zeta-Globin chain expression in carriers of a number of deletional alpha-thalassemias is investigated by radioimmunoassay. In a few cases, zeta-globin mRNAs are also studied. zeta-Globin chains are detected in (--SEA/), (--MED/), and (--SPAN/) deletions, but not in six other deletional mutations. These results suggest that the DNA element capable of suppressing zeta-globin expression in adult erythroid cells is present within the (--SPAN/) deletion, while the DNA fragment between the 5' breakpoints of the (--SA/) and the (--SEA/) deletions may contain sequences necessary for augmenting zeta-globin expression in adult erythroid cells. Furthermore, zeta-globin chains are shown by an immunocytologic technique to be present in all circulating erythrocytes in carriers of the (--SEA/) and (--MED/) deletions. This simple immunocytologic test is highly sensitive and specific to detect adult carriers of either the (--SEA/) or (--MED/) deletions, and can be used for the detection of couples at risk of pregnancies involving fetuses with homozygous alpha-thalassemia.     

Baseline Socio-demographic Characteristics and Self-Reported Diet and Physical Activity Shifts Among Recent Immigrants Participating in the Randomized Controlled Lifestyle Intervention: “Live Well”

The goal of this paper is to describe the baseline characteristics of Live Well (intervention to prevent weight gain in recent immigrant mother–child dyads from Brazil, Haiti, and Latin America) participants, and to explore self-reported changes in diet and physical activity post-immigration. Baseline data from 383 mothers were used for this study. Dyads attended a measurement day where they completed self-administered surveys collecting information about socio-demographics, diet, physical activity, other psychosocial variables, and height and weight. Haitian mothers’ socio-demographic profile differed significantly from that of Brazilians’ and Latinas’: they have been in the US for a shorter period of time, have higher rates of unemployment, are less likely to be married, more likely to have ≥3 children, more likely to be obese, and have immigrated for family or other reasons. In multivariate models, self-reported changes in diet and physical activity since migrating to the US were significantly associated with BMI with non-linear relationships identified. Future research is needed to understand how diet and physical activity change while acculturating to the US and explore the adoption of both healthy and unhealthy dietary changes.     

On the origin of enhanced sensitivity in nanoscale FET-based biosensors

Electrostatic counter ion screening is a phenomenon that is detrimental to the sensitivity of charge detection in electrolytic environments, such as in field-effect transistor-based biosensors. Using simple analytical arguments, we show that electrostatic screening is weaker in the vicinity of concave curved surfaces, and stronger in the vicinity of convex surfaces. We use this insight to show, using numerical simulations, that the enhanced sensitivity observed in nanoscale biosensors is due to binding of biomolecules in concave corners where screening is reduced. We show that the traditional argument, that increased surface area-to-volume ratio for nanoscale sensors is responsible for their increased sensitivity, is incorrect.In recent years, there has been a major drive to use field-effect transistor (FET)-based devices to detect biological molecules in electrolytic environments (1). These biosensors use the charge of biomolecules to gate the current through a transistor (2). Frequently, the transistor is based on a quasi-1D nanostructure, such as a nanowire (NW) or nanotube, and the biomolecules bind directly to the surface of the nanoscale structure (1, 3). The use of such nanostructures is justified by the belief that nanoscale biosensors are more sensitive, with sensitivity defined as the relative change in drain current or a shift in threshold voltage in response to a change in bound biomolecule density. A few experiments specifically studied the effect of shrinking nanowire radii on sensitivity, albeit with varying structures, analytes, and sensing circumstances, and found that shrinking a sensor’s dimensions indeed improves its sensitivity (4–6). The enhanced sensitivity has been loosely attributed to the increase in the sensor’s surface area-to-volume ratio, which is a direct result of shrinking its dimensions. This argument has been analytically justified in the context of gas sensors (7). However, there is a fundamental difference between gas and biomolecule sensing: biomolecule sensing is performed in an electrolyte, and the ions therein will screen the charge of bound biomolecules in a phenomenon known as Debye screening (8, 9). The direct application of the gas sensing result to the biosensing environment implicitly assumes that the screening effect does not change with shrinking dimensions, an assumption we believe to be false. There have been studies that included a rigorous treatment of screening in biosensors, but they studied neither the specific cause of increased sensitivity at the nanoscale, nor the effect of varying size on screening behavior (10). We believe the phenomenon responsible for the increased sensitivity of nanowires in particular, and nanostructured biosensors in general, have not yet been uncovered by the research community.We have previously dissected the operation of biosensors into two independent parts to better understand the underlying physics (11): first, biomolecule charges cause a change in the local electrostatic potential at the outer surface of the gate dielectric. This potential change in turn causes a change in the drain current of the underlying semiconductor channel. The latter part is simply the transconductance effect of an FET-based transistor; nanoscale biosensors have no advantage in this respect over planar sensors. The nanoscale advantage should therefore lie in the first part of the sensor operation, which is a capacitive transduction effect, dominated by the capacitance of the Debye screening layer. We therefore believe understanding screening behavior at the nanoscale is key to understanding the behavior of nanoscale biosensors.In this paper, we revisit screening near curved nanostructure surfaces by solving the Poisson–Boltzmann equation that led to the original Debye–Hückel formalism. Our simple analytical arguments will show that screening is stronger near surfaces with convex curvature, and weaker near surfaces with concave curvature. We only consider simple convex and concave surfaces because almost all nonplanar surfaces can be decomposed into local areas with either convex or concave curvature.Next, we apply the basic insight we gain from the previous step to understand and analyze the specific case of nanowire biosensors. Increasing the surface area-to-volume ratio of nanowire sensors actually means increasing their convexity, which should result in increased Debye screening and reduced sensitivity. However, nanowires placed on insulating substrates create concave corners between the nanowire and the substrate. We believe biomolecules bound in such concave corners are responsible for the increased sensitivity experimentally observed in nanowires.     

Oncogenic BRAF and KRAS mutations in endosalpingiosis

Endosalpingiosis, a microscopic lesion composed of ectopic Fallopian tube epithelium, frequently involves the peritoneum and lymph nodes in patients with ovarian serous borderline tumour or low-grade serous carcinoma, but its pathogenic significance remains unclear. Using laser-capture microdissection and droplet digital PCR, we investigated whether endosalpingiosis harbours the driver mutations in BRAF and KRAS that characterise ovarian low-grade serous neoplasms. Somatic mutations were detected in 14 (33%) of 43 endosalpingiotic lesions analysed. Of 21 women with endosalpingiosis associated with a synchronous or metachronous ovarian low-grade serous tumour, mutations were identified in endosalpingiotic lesions from 11 (52%) women, with most cases (10/11, 91%) demonstrating identical mutations in both tumour and endosalpingiosis. In contrast, of 13 cases of endosalpingiosis not associated with an ovarian tumour, only one harboured a KRAS mutation. The proliferative activity as assessed by Ki-67 immunohistochemistry was lower in endosalpingiosis than in low-grade serous tumours, and endosalpingiosis with either a BRAF or KRAS mutation had a significantly lower Ki-67 index than those without. Ectopic expression of KRAS^G12V in Fallopian tube epithelial cells led to ERK phosphorylation, p21 induction, growth arrest and cellular senescence. In conclusion, we demonstrate that endosalpingiosis represents an interesting example of cancer driver mutations in deceptively normal-appearing cells, which may be prone to neoplastic transformation upon bypass of endogenous oncosuppressive mechanisms. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

第四跖背动脉逆行岛状皮瓣在第二足趾再造手指供区趾蹼皮肤缺损中的临床应用

目的探讨第四跖背动脉逆行岛状皮瓣修复第二足趾再造手指后供区趾蹼皮肤缺损的临床应用效果。方法2007年1月~2009年12月,均为切取第二足趾再造手指时携带面积不等的跖背皮瓣13例患者的临床资料进行分析。结果术后13例转移皮瓣全部存活,术后随访时间为3~16个月,皮瓣质地、感觉良好,趾蹼外形满意,供足行走功能满意。结论最大限度地保护了供足的功能,减少了植皮后并发症,是较为理想的手术方式。     

Imaging of vitreous cortex hyalocyte dynamics using non-confocal quadrant-detection adaptive optics scanning light ophthalmoscopy in human subjects

Vitreous cortex hyalocytes are resident macrophage cells that help maintain the transparency of the media, provide immunosurveillance, and respond to tissue injury and inflammation. In this study, we demonstrate the use of non-confocal quadrant-detection adaptive optics scanning light ophthalmoscopy (AOSLO) to non-invasively visualize the movement and morphological changes of the hyalocyte cell bodies and processes over 1-2 hour periods in the living human eye. The average velocity of the cells 0.52 ± 0.76 µm/min when sampled every 5 minutes and 0.23 ± 0.29 µm/min when sampled every 30 minutes, suggesting that the hyalocytes move in quick bursts. Understanding the behavior of these cells under normal physiological conditions may lead to their use as biomarkers or suitable targets for therapy in eye diseases such as diabetic retinopathy, preretinal fibrosis and glaucoma.