Bioarchaeological evidence for adaptive plasticity and constraint: Exploring life‐history trade‐offs in the human past

The Developmental Origins of Health and Disease paradigm evaluates the consequences of early life stress on health at later stages of life. Interacting with this paradigm represents a profound opportunity to leverage the lifespan and contextual approaches to human skeletal remains adopted by bioarchaeological research. Teeth and bone provide evidence for stressors experienced early in life. These events represent evidence for adaptive plasticity as Individuals survive the events through reallocation of energy to essential physiological functions, which inhibits enamel and skeletal growth. Age‐at‐death, adult body size, chronic infection, or childhood mortality may be used as covariates to better understand the physiological constraints operating on individual bodies following survival of early life stress. Contextual evidence from cemeteries provides clues to the ecological and cultural contingencies that exacerbate or mitigate the expression of these trade‐offs. Future studies should incorporate newly derived methods that provide reproducible and precise ways to evaluate early life stress, while incorporating populations that are often neglected.     

超声引导下髂筋膜神经阻滞联合全麻对老年股骨近端骨折患者术后血清疼痛介质PGE2、SP和认知功能及睡眠质量的影响

摘要 目的：观察超声引导下髂筋膜神经阻滞联合全麻对老年股骨近端骨折患者术后血清疼痛介质前列腺素E₂（PGE₂）、P物质（SP）和认知功能及睡眠质量的影响。方法：选取2018年8月~2021年9月期间我院收治的择期行手术治疗的老年股骨近端骨折患者80例,根据随机数字表法分为对照组（40例,常规全麻方案）和观察组（40例,超声引导下髂筋膜神经阻滞联合全麻方案）,对比两组麻醉效果、血流动力学、疼痛情况、认知功能和睡眠质量,观察不同模式麻醉下的安全性。结果：观察组的苏醒及拔管时间均短于对照组,丙泊酚使用量少于对照组（P<0.05）。两组置入喉罩时（T1）~术毕时（T3）心率（HR）先升高后下降,平均动脉压（MAP）先下降后升高（P<0.05）;观察组T1~T3时点HR低于对照组,MAP高于对照组（P<0.05）。两组术后24 h血清PGE₂、SP水平和视觉疼痛模拟量表（VAS）评分均升高,但观察组低于对照组（P<0.05）。两组术后1 d、2 d、3 d 蒙特利尔认知评估量表（MoCA）评分较术前先下降后升高（P<0.05）;观察组术后2 d、3 d MoCA评分高于对照组（P<0.05）。两组术后1 d、2 d、3 d匹兹堡睡眠质量评估量表（PSQI）评分较术前先升高后下降（P<0.05）;观察组术后1 d、2 d、3 d PSQI评分低于对照组（P<0.05）。两组不良反应发生率对比无差异（P>0.05）。结论：老年股骨近端骨折患者术中选用超声引导下髂筋膜神经阻滞联合全麻,镇痛效果显著,可稳定机体血流动力学,减少对认知功能和睡眠质量的影响,且安全性良好。     

TLR4-dependent upregulation of the platelet NLRP3 inflammasome promotes platelet aggregation in a murine model of hindlimb ischemia

Platelets play a critical role in the pathophysiology of peripheral arterial disease (PAD). The mechanisms by which muscle ischemia regulates aggregation of platelets are poorly understood. We have recently identified the Nod-like receptor nucleotide-binding domain leucine rich repeat containing protein 3 (NLRP3) expressed by platelets as a critical regulator of platelet activation and aggregation, which may be triggered by activation of toll-like receptor 4 (TLR4). In this study, we performed femoral artery ligation (FAL) in transgenic mice with platelet-specific ablation of TLR4 (TLR4 PF4) and in NLRP3 knockout (NLRP3^?/?) mice. NLRP3 inflammasome activity of circulating platelets, as monitored by activation of caspase-1 and cleavage of interleukin-1β (IL-1β), was upregulated in mice subjected to FAL. Genetic ablation of TLR4 in platelets led to decreased platelet caspase 1 activation and platelet aggregation, which was reversed by the NLRP3 activator Nigericin. Two weeks after the induction of FAL, ischemic limb perfusion was increased in TLR4 PF4 and NLRP3^?/? mice as compared to control mice. Hence, activation of platelet TLR4/NLRP3 signaling plays a critical role in upregulating platelet aggregation and interfering with perfusion recovery in muscle ischemia and may represent a therapeutic target to improve limb salvage.     

A possible balance of magnesium accumulations among bone, cartilage, artery, and vein in single human individuals

It is known that a large quantity of magnesium contains bones, and the magnesium contents in spongy bones decrease gradually with advancing age. To elucidate the relationships between a decrease of mineral contents in human bones and an accumulation of minerals in the other human tissues, the content of magnesium was analyzed by inductively coupled plasma-atomic emission spectrometry among human bones, arteries, veins, and cartilages in 27 subjects (17 men and 10 women). These were resected from the subjects who died in the age range 40–98 yr. Calcanei were chosen for analysis of magnesium contents in contrast with femoral, popliteal, and common carotid arteries, internal jugular and femoral veins, superior and inferior venae cavae, and pubic symphyses. The magnesium contents in the calcanei decreased gradually with aging, whereas they increased progressively in the arteries, veins, and pubic symphyses with aging. It was found that as the magnesium contents decreased in the calcanei, they increased in the arteries, such as the femoral, popliteal, and common carotid arteries, whereas they decreased inversely in the veins, such as the internal jugular and femoral veins and superior and inferior venae cavae. Furthermore, as the magnesium contents decreased in the calcanei, they hardly changed in the pubic symphyses. These suggest that magnesium released from bones is accompanied by accumulation of magnesium in the arteries.     

Scd1 ab-Xyk : a new asebia allele characterized by a CCC trinucleotide insertion in exon 5 of the stearoyl-CoA desaturase 1 gene in mouse

We describe here a spontaneous, autosomal recessive mutant mouse suffering from skin and hair defects, which arose in the outbred Kunming strain. By haplotype analysis and direct sequencing of PCR products, we show that this mutation is a new allele of the asebia locus with a naturally occurring mutation in the Scd1 gene (a CCC insertion at nucleotide position 835 in exon 5), which codes for stearoyl-CoA desaturase 1. This mutation introduces an extra proline residue at position 279 in the Scd1 protein. The mutant mice, originally designated km/km but now assigned the name Scd1 ^ab-Xyk (hereafter abbreviated as ab ^Xyk / ab ^Xyk ), have a similar gross and histological phenotype to that reported for previously characterized allelic asebia mutations ( Scd1 ^ab , Scd1 ^abJ , Scd1 ^ab2J , and Scd1 ^tm1Ntam ). Histological analysis showed they were also characterized by hypoplasic sebaceous glands and abnormal hair follicles. In a cross between Kunming- ab ^Xyk / ab ^Xyk and ABJ/Le- ab ^J / ab ^J mice, all the progeny showed the same phenotype, indicating that the two mutations were non-complementing and therefore allelic. Comparisons with the other four allelic mutants indicate that the Scd1 ^ab-Xyk mutation causes the mildest change in Scd1 function. This new mouse mutant is a good model not only for the study of scarring alopecias in humans, which are characterized by hypoplasic sebaceous glands, but also for studying the structure and function of the Scd1 protein.Communicated by G. ReuterThe first two authors contribute equally to this work     

Insights from stable light isotopes on enamel defects and weaning in Pliocene herbivores

A high prevalence of enamel hypoplasia in several herbivores from the early Pliocene Langebaanweg locality, South Africa, indicates general systemic stress during the growing years of life. The presence of several linear enamel hypoplasias per tooth crown in many teeth further suggest that these stress events may be episodic. The δ¹⁸O values along tooth crowns of mandibular second molars ofSivatherium hendeyi (Artiodactyla, Giraffidae) were used to investigate the cause of the stress events in this tooth type. Results show that weaning in this fossil giraffid occurred at a similar ontogenetic age to that in extant giraffes, and that the observed enamel hypoplasia towards the base of this tooth type manifested post-weaning. Further, high-resolution oxygen isotope analyses acrossS. hendeyi third molars suggest that the entire development of defective tooth crowns occurred under conditions of increased aridity in which the cool, rainy part of the seasonal cycle was missing. The high prevalence of this defect in many herbivores suggests that climatic conditions were not favourable. This study reiterates the value of stable isotope analyses in determining both the behaviour of fossil animals and the environmental conditions that prevailed during tooth development.     

Correlations of calcium accumulations in arteries, veins, cartilages, ligaments, and bones in single humans

To show the relationships of calcium accumulation in the thoracic aorta to the other tissues, calcium contents were determined with a microwave-induced plasma-atomic emission spectrometer on arteries, veins, cartilages, ligaments, and bones. These tissues were resected from 18 individuals, consisting of 11 men and 7 women who died in the age range 59–91 yr. As thoracic and abdominal aortas are routinely used for radiographic examination of arterial calcification, they appear to be standard tissues of the calcium accumulation. The calcium accumulations were determined in the femoral artery, the superior and inferior venae cavae, the internal jugular vein, cartilages of the articular disk of the temporomandibular joint and the intervertebral disk, both the ligaments of the anterior cruciate ligament and the ligamentum capitis femoris, and the calcaneus, in contrast with the thoracic aorta. As calcium increased in the thoracic aorta, it increased in the femoral artery, the articular disk of the temporomandibular joint, the intervertebral disk, both ligaments of the anterior cruciate ligament, and the ligamentum capitis femoris, but it did not increase in veins, such as the superior and inferior venae cavae and the internal jugular vein. In contrast, it decreased in the calcaneus.     

Markers of physiological stress in juvenile bonobos (Pan paniscus): Are enamel hypoplasia,skeletal development and tooth size interrelated?

A reduction in enamel thickness due to disrupted amelogenesis is referred to as enamel hypoplasia (EH). Linear EH in permanent teeth is a widely accepted marker of systemic physiological stress. An enigmatic, nonlinear form of EH commonly manifest in great ape and human deciduous canines (dc) is known as localized hypoplasia of primary canines (LHPC). The etiology of LHPC and what it signifies—localized traumatic or systemic physiological stress—remains unclear. This report presents frequency data on LHPC, hypostotic cranial traits, and tooth size in a sample of juvenile bonobos, then tests hypotheses of intertrait association that improve knowledge of the etiology and meaning of LHPC. The fenestration hypothesis is tested using hypostotic cranial traits as a proxy for membrane bone ossification, and the relationship between tooth size, LHPC, and hypostosis is investigated. Macroscopic observations of EH, hypostotic traits, and measurements of buccolingual tooth size were conducted according to established standards. LHPC was found in 51.2% of bonobos (n = 86) and in 26% of dc teeth (n = 269). Hypostotic traits were observed in 55.2% of bonobos (n = 96). A test of the association between LHPC and hypostosis yielded nonsignificant results (χ² = 2.935; P = 0.0867). Primary canines were larger in specimens with LHPC than in unaffected specimens (paired samples t test; udc, P = 0.011; ldc, P = 0.018), a result consistent with the fenestration hypothesis of LHPC pathogenesis. Hypostosis was not associated with differences in tooth size (P > 0.05). LHPC may be an indirect indicator of physiological stress, resulting from large, buccally displaced primary canines. Am J Phys Anthropol, 2009. © 2008 Wiley‐Liss, Inc.     

Dietary variation and stress among prehistoric Jomon foragers from Japan

Current archaeological evidence indicates that greater dietary reliance on marine resources is recorded among the eastern Jomon, while plant dependence prevailed in western/inland Japan. The hypothesis that the dietary choices of the western/inland Jomon will be associated with greater systemic stress is tested by comparing carious tooth and enamel hypoplasia frequencies between the eastern and western/inland Jomon. Demographic collapse coincides with climate change during the Middle to Late Jomon period, suggesting dwindling resource availability. It is hypothesized that this change was associated with greater systemic stress and/or dietary change among the Middle to Late Jomon. This hypothesis is tested by comparing enamel hypoplasia and carious tooth frequencies between Middle to Late and Late to Final Jomon foragers. Enamel hypoplasia was significantly more prevalent among the western/inland Jomon. Such findings are consistent with archaeological studies that argue for greater plant consumption and stresses associated with seasonal resource depletion among the western/inland Jomon. Approximately equivalent enamel hypoplasia frequencies between Middle to Late and Late to Final Jomon foragers argues against a demographic collapse in association with diminished nutritional returns. Significant differences in carious tooth frequencies are, however, observed between Middle to Late and Late to Final Jomon foragers. These results suggest a subsistence shift during the Middle to Late Jomon period, perhaps in response to a changed climate. The overall patterns of stress documented by this study indicate wide-spread environmentally directed biological variation among the prehistoric Jomon.