Characterization of an immune deficiency homolog (IMD) in shrimp (Fenneropenaeus chinensis) and crayfish (Procambarus clarkii)

The immune deficiency (IMD) signal pathway mediates immunity against Gram-negative bacteria in Drosophila. Recent studies show that the IMD pathway also involves in antiviral innate immune responses. The functions of the pathway in crustacean immunity are largely unknown. In this paper, two IMDs (FcIMD and PcIMD), one of the key elements of the IMD pathway, were identified from Chinese white shrimp Fenneropenaeus chinensis and red swamp crayfish Procambarus clarkii. Both proteins have a death domain located at the C-terminal. FcIMD was mainly expressed in the gills and stomach and PcIMD was mainly detected in the heart, hepatopancreas, and stomach. FcIMD peaked in hemocytes at 12 h after white spot syndrome virus (WSSV) challenge and it peaked in the gills at 6 h after WSSV challenge, but it was decreased at 2 h and kept the low level to 24 h in hemocytes and no obviously change in gill after Vibrio anguillarum challenge. PcIMD first decreased in hemocytes at 2 h and peaked at 12 h in hemocytes after V. anguillarum challenge. It was also upregulated in gill after bacterial challenge, peaked at 2 h, and decreased at 6 h, and then gradually increased at 12–24 h. PcIMD has no significant change in hemocytes and gill after WSSV challenge. Western blot analysis detected FcIMD protein in all tissues, and immunocytochemical analysis localized FcIMD in the cytoplasm of hemocytes. RNA interference analysis showed that the IMD pathway was involved in regulating the expression of three kinds AMP genes, including crustins, anti-lipopolysaccharide factors and lysozymes, in shrimp and crayfish. They are Cru 1, Cru 2, ALF 1, ALF 2 and Lys 1 in crayfish, and Cru1, Cru 3, ALF 6, ALF 8, and Lys2 in shrimp. These results suggest that although IMD distribution and expression patterns have some differences, the IMD pathway may have conserved function for AMP regulation in shrimp and crayfish immunity against Gram-negative bacteria.     

Efficiency of immunoglobulin G replacement therapy in common variable immunodeficiency: correlations with clinical phenotype and polymorphism of the neonatal Fc receptor

Treatment of common variable immunodeficiency disorders (CVID) is based on replacement therapy using intravenous (i.v.) or subcutaneous (s.c.) immunoglobulin (Ig)G. Interindividual variation of IgG dose is common. A total of 380 CVID patients on stable IgG replacement from two prospective cohorts were analysed. An ‘efficiency’ index was defined as the ratio of serum IgG trough level minus IgG residual to the average weekly dose of IgG infusion. A reduced efficiency of IgG was associated independently with the i.v. route (P < 0·001) and with the presence of at least one CVID disease‐related phenotype (lymphoproliferation, autoimmune cytopenia or enteropathy) (P < 0·001). High IgG efficiency was noted in patients homozygotes for the variable number tandem repeat (VNTR) 3/3 polymorphism of the neonatal Fc receptor gene [IgG Fc fragment receptor transporter alpha chain (FCGRT)] promoter, and this was particularly significant in patients treated with IVIG (P < 0.01). In a multivariate analysis, FCGRT VNTR 3/3 genotype (P = 0·008) and high serum albumin (P < 0·001) were associated independently with increased efficiency of i.v. Ig.     

Circulating phenotypic B‐1 cells are decreased in common variable immunodeficiency and correlate with immunoglobulin M levels

B‐1 cells are innate‐like lymphocytes characterized by spontaneous production of ‘natural’ polyspecific antibodies, often of self‐specificity, and thought to be responsible for tissue homeostasis, mucosal protection, maintaining resting serum immunoglobulin (Ig)M levels and for early immunoglobulin production following infection. Although defined most clearly in mice, a human B‐1 cell counterpart, defined by the phenotype CD19 or 20⁺CD27⁺CD43⁺CD69 or 70^–, has been proposed recently, facilitating a study of their role in human humoral immunodeficiencies, such as common variable immunodeficiency (CVID). This study examined circulating B‐1 cells in 27 CVID patients in comparison to age‐matched controls (n = 28). Phenotypic putative B‐1 cell proportions varied widely, but there was an overall 60–70% decrease in CVID (0·039 ± 0·033% of lymphocytes, mean ± standard deviation) compared with controls (0·110 ± 0·159% of lymphocytes, P = 0·0012). This decrease was, however, explained largely by concomitant loss of total CD27⁺ memory B cells characteristic of CVID, although those with higher memory B cell proportions appeared to show a true decrease. No age‐related effects were apparent in B‐1 cell proportions. However, among CVID patients, there was a strong positive correlation between the B‐1 cell proportion and serum IgM levels, a relationship that was not evident for IgA, nor was there a relationship between memory B cell proportions and serum IgM. Patients with CVID have fewer circulating putative phenotypic B‐1 cells, which largely reflected the overall decrease in memory B cells. However, B‐1 cell proportions correlated with resting serum IgM levels, suggesting a possible role in IgM deficiency in CVID.     

头颅CT检查在新兵体格复检中的价值

 目的 分析探讨头颅CT检查在新兵体格复检中的价值和必要性。方法 回顾性分析武警某部2482名体格复查新兵的头颅CT结果。结果 检出颅内病变共224例(阳性率9.03%)。其中颅内蛛网膜囊肿110例(阳性率4.43%),透明隔间腔或囊肿63例(阳性率2.54%),副鼻窦炎21例(阳性率0.85%),脑内非生理性钙化19例(阳性率0.77%),脑室系统发育异常5例(阳性率0.20%),脑软化灶3例(阳性率0.12%),颅内肿瘤2例(阳性率0.08%),颅骨骨瘤1例(阳性率0.04%)。结论 头颅CT检查能有效排查出新兵头颅内病灶,为降低伤病残率奠定基础,建议列为新兵体格复查项目。     

Robustness of a Combined Modified Dixon and PROPELLER Sequence with Two Interleaved Echoes in Clinical Head and Neck MRI

Purpose:The combination of modified Dixon (mDixon) and periodically rotated overlapping parallel lines with enhanced reconstruction sequence with two interleaved echoes, which promotes uniform fat-suppression and motion insensitivity, has recently become available for commercial magnetic resonance imaging (MRI) scanners. To compare the robustness of this combination sequence with that of standard Cartesian mDixon sequence for fat-suppressed T₂-weighted imaging in clinical head and neck MRI.Methods:Fifty patients with head and neck tumors were involved this study. All patients underwent MRI using both the combination and standard sequences. Two radiologists independently scored motion artifacts and water–fat separation error using a 4-point scale (1, unacceptable; 4, excellent). Furthermore, comprehensive comparative evaluation was performed using a 5-point scale (1, substantially inferior; 5, substantially superior). Data were statistically analyzed using the Wilcoxon signed-rank test.Results:In the motion artifact assessment, ratings of 3 or 4 points were assigned to 45% (observer-1, 58.0%; observer-2, 32.0%) and 97% (100%; 94.0%) of images for the standard and combination sequences, respectively (P < 0.001). For the water–fat separation error assessment, ratings of 3 or 4 points were assigned to 100% (100%; 100%) and 85% (84.0%; 86.0%) of images, respectively (P < 0.001). In the comprehensive evaluation, of the 100 cases (observer-1, 50; observer-2, 50), 96 were rated at four or five points. In cases with slight or no motion artifacts and water–fat separation errors, the combination sequence was superior to the standard sequence in term of noise and sharpness, and equal in terms of contrast.Conclusion:Although water–fat separation errors increased significantly in the combination sequence, most of these were acceptable. The significantly decreased motion artifacts in the combination sequence significantly improved image quality overall.     

Dorsal Raphe Dopamine Neurons Signal Motivational Salience Dependent on Internal State,Expectation, and Behavioral Context

The ability to recognize motivationally salient events and adaptively respond to them is critical for survival. Here, we tested whether dopamine (DA) neurons in the dorsal raphe nucleus (DRN) contribute to this process in both male and female mice. Population recordings of DRN^DA neurons during associative learning tasks showed that their activity dynamically tracks the motivational salience, developing excitation to both reward-paired and shock-paired cues. The DRN^DA response to reward-predicting cues was diminished after satiety, suggesting modulation by internal states. DRN^DA activity was also greater for unexpected outcomes than for expected outcomes. Two-photon imaging of DRN^DA neurons demonstrated that the majority of individual neurons developed activation to reward-predicting cues and reward but not to shock-predicting cues, which was surprising and qualitatively distinct from the population results. Performing the same fear learning procedures in freely-moving and head-fixed groups revealed that head-fixation itself abolished the neural response to aversive cues, indicating its modulation by behavioral context. Overall, these results suggest that DRN^DA neurons encode motivational salience, dependent on internal and external factors.SIGNIFICANCE STATEMENT Dopamine (DA) contributes to motivational control, composed of at least two functional cell types, one signaling for motivational value and another for motivational salience. Here, we demonstrate that DA neurons in the dorsal raphe nucleus (DRN) encode the motivational salience in associative learning tasks. Neural responses were dynamic and modulated by the animal''s internal state. The majority of single-cells developed responses to reward or paired cues, but not to shock-predicting cues. Additional experiments with freely-moving and head-fixed mice showed that head-fixation abolished the development of cue responses during fear learning. This work provides further characterization on the functional roles of overlooked DRN^DA populations and an example that neural responses can be altered by head-fixation, which is commonly used in neuroscience.     

Novel ACOX1 mutations in two siblings with peroxisomal acyl-CoA oxidase deficiency

Peroxisomal acyl-CoA oxidase (ACOX1) deficiency is a rare autosomal recessive single enzyme deficiency characterized by hypotonia, seizures, failure to thrive, developmental delay, and neurological regression starting from approximately 3 years of age.Here, we report two siblings with ACOX1 deficiency born to non-consanguineous Japanese parents. They showed mild global developmental delay from infancy and began to regress at 5 years 10 months and 5 years 6 months of age respectively. They gradually manifested with cerebellar ataxia, dysarthria, pyramidal signs, and dysphasia. Brain MRI revealed T2 high-intensity areas in the cerebellar white matter, bilateral middle cerebellar peduncle, and transverse tracts of the pons, followed by progressive atrophy of these areas.Intriguingly, the ratios of C24:0, C25:0, and C26:0 to C22:0 in plasma, which usually increase in ACOX1 deficiency were within normal ranges in both patients. On the other hand, whole exome sequencing revealed novel compound heterozygous variants in ACOX1: a frameshift variant (c.160delC:p.Leu54Serfs*18) and a missense variant (c.1259 T > C:p.Phe420Ser). The plasma concentration of individual very long chain fatty acids (C24:0, C25:0, and C26:0) was elevated, and we found that peroxisomes in fibroblasts of the patients were larger in size and fewer in number as previously reported in patients with ACOX1 deficiency. Furthermore, the C24:0 β-oxidation activity was dramatically reduced.Our findings suggest that the elevation of individual plasma very long chain fatty acids concentration, genetic analysis including whole exome analysis, and biochemical studies on the patient’s fibroblasts should be considered for the correct diagnosis of ACOX1 deficiency.     

Photoparoxysmal response in ADCK3 autosomal recessive ataxia: a case report and literature review

Mutations in AarF domain‐containing kinase 3 (ADCK3) are responsible for the most frequent form of hereditary coenzyme Q10 (CoQ10) deficiency (Q10 deficiency‐4), which is mainly associated with autosomal recessive cerebellar ataxia type 2 (ARCA2). Clinical presentation is characterized by a variable degree of cerebellar atrophy and a broad spectrum of associated symptoms, including muscular involvement, movement disorders, neurosensory loss, cognitive impairment, psychiatric symptoms and epilepsy. In this report, we describe, for the first time, a case of photoparoxysmal response in a female patient with a mutation in ADCK3. Disease onset occurred in early childhood with gait ataxia, and mild‐to‐moderate degeneration. Seizures appeared at eight years and six months, occurring only during sleep. Photoparoxysmal response was observed at 14 years, almost concomitant with the genetic diagnosis (c.901C>T;c.589‐3C>G) and the start of CoQ10 oral supplementation. A year later, disease progression slowed down, and photosensitivity was attenuated. A review of the literature is provided focusing on epileptic features of ADCK3‐related disease as well as the physiopathology of photoparoxysmal response and supposed cerebellar involvement in photosensitivity. Moreover, the potential role of CoQ10 oral supplementation is discussed. Prospective studies on larger populations are needed to further understand these data.     

肱骨大结节上方的解剖分型及临床意义

目的 通过对肱骨大结节上面观的形态学分型,探讨其临床意义。 方法 将296例肩关节CT扫描图像根据大结节上面观形态进行分型,分别测量冈上肌、冈下肌和小圆肌肌腱在大结节上的止点长度,肩胛下肌肌腱在小结节上的止点长度,大结节最高点至肱骨头最高点的距离以及结节间沟的宽度和深度。 结果 肱骨大结节上面观形态可分为3型：弧形45.60%（135例）,平坦形44.26%（131例）,丘形10.14%（30例）。弧形的肱骨大结节,其冈上肌肌腱止点长度短于平坦形和丘形;丘形的肱骨大结节,其冈上肌肌腱在大结节上的止点长度、肩胛下肌肌腱在小结节上的止点长度、结节间沟的宽度和深度均短于弧形和平坦形;丘形的大结节最高点至肱骨头最高点的距离大于弧形和平坦形,差异均有统计学意义（P＜0.05）,其他解剖学形态差异无统计学意义（P>0.05）。 结论 不同分型的肱骨大结节上面观对临床肱骨大结节相关疾病诊治有一定的指导意义。     

儿童肱骨髁上骨折相关的神经损伤研究进展

肱骨髁上骨折常见于7岁以下儿童,约占儿童肢体骨折的30%和肘部骨折的50%~70%;根据受伤机制的不同可分为伸直型和屈曲型,其中伸直型约占96%~98%、屈曲型约占2%~4%,是最常见的儿童骨折之一[1,2]。Gartland分型是目前应用最广泛的肱骨髁上骨折分型系统:Ⅰ型骨折无移位常采取保守治疗,Ⅱ型和Ⅲ型骨折因创伤严重致治疗棘手。由于儿童肱骨远端特殊的解剖生理特点,尺神经、正中神经及桡神经均容易损伤,文献报道肱骨髁上骨折导致的神经损伤发生率高达10%~20%[1-3],医源性神经损伤也高达3%~6%[2-4],给临床带来严重挑战。本文就儿童肱骨髁上骨折伴神经损伤的研究进展作一综述。