Phenotype and Micro-array characterization of duplication 11q22.1-q25 and review of the literature

Partial duplication of 11q is related to several malformations like growth retardation, intellectual disability, hypoplasia of corpus callosum, short nose, palate defects, cardiac, urinary tract abnormalities and neural tube defects. We have studied the clinical and molecular characteristics of a patient with severe intellectual disabilities, dysmorphic features, congenital inguinal hernia and congenital cerebral malformation which is referred to as cytogenetic exploration. We have used FISH and array CGH analysis for a better understanding of the double chromosomic aberration involving a 7p microdeletion along with a partial duplication of 11q due to adjacent segregation of a paternal reciprocal translocation t(7;11)(p22;q21) revealed after banding analysis. The patient's karyotype formula was: 46,XY,der(7)t(7;11)(p22;q21)pat. FISH study confirmed these rearrangement and array CGH technique showed precisely the loss of at least 140 Kb on chromosome7p22.3pter and 33.4 Mb on chromosome11q22.1q25. Dysmorphic features, severe intellectual disability and brain malformations could result from the 11q22.1q25 trisomy. Our study provides an additional case for better understanding and delineating the partial duplication 11q.     

Multitargeted therapies for multiple myeloma

Multiple myeloma (MM) comprises 1% of all malignancies and 10% of all hematological malignancies. MM is a malignancy of plasma cells in the bone marrow where complex and dynamic interactions with the bone marrow microenvironment lead to tumor progression, skeletal destruction and angiogenesis. Despite the discovery of several novel treatments against MM, including the proteasome inhibitor bortezomib, it is considered to be an incurable disease with an average 4–5 years overall survival.     

Identification and fine mapping of <Emphasis Type="Italic">Pi33</Emphasis>, the rice resistance gene corresponding to the Magnaporthe grisea avirulence gene <Emphasis Type="Italic">ACE1</Emphasis>

Rice blast disease is a major constraint for rice breeding. Nevertheless, the genetic basis of resistance remains poorly understood for most rice varieties, and new resistance genes remain to be identified. We identified the resistance gene corresponding to the cloned avirulence gene ACE1 using pairs of isogenic strains of Magnaporthe grisea differing only by their ACE1 allele. This resistance gene was mapped on the short arm of rice chromosome 8 using progenies from the crosses IR64 (resistant) × Azucena (susceptible) and Azucena × Bala (resistant). The isogenic strains also permitted the detection of this resistance gene in several rice varieties, including the differential isogenic line C101LAC. Allelism tests permitted us to distinguish this gene from two other resistance genes [Pi11 and Pi-29(t)] that are present on the short arm of chromosome 8. Segregation analysis in F₂ populations was in agreement with the existence of a single dominant gene, designated as Pi33. Finally, Pi33 was finely mapped between two molecular markers of the rice genetic map that are separated by a distance of 1.6 cM. Detection of Pi33 in different semi-dwarf indica varieties indicated that this gene could originate from either one or a few varieties.Communicated by D.J. Mackill     

p33(ING1) enhances UVB-induced apoptosis in melanoma cells

The biological functions of the tumor suppressor ING1 have been studied extensively in the past few years since it was cloned. It shares many biological functions with p53 and has been reported to mediate growth arrest, senescence, apoptosis, anchorage-dependent growth, chemosensitivity, and DNA repair. Some of these functions, such as cell cycle arrest and apoptosis, have been shown to be dependent on the activity of both ING1 and p53 proteins. Two recent reports by Scott and colleagues demonstrate that p33(ING1) (one of the ING1 isoforms) translocates to the nucleus and binds to PCNA upon UV irradiation. Here we report that p33(ING1) mediates UV-induced cell death in melanoma cells. We found that overexpression of p33(ING1) increased while the introduction of an antisense p33(ING1) plasmid reduced the apoptosis rate in melanoma cells after UVB irradiation. We also demonstrated that enhancement of UV-induced apoptosis by p33(ING1) required the presence of p53. Moreover, we found that p33(ING1) enhanced the expression of endogenous Bax and altered the mitochondrial membrane potential. Taken together, these observations strongly suggest that p33(ING1) cooperates with p53 in UVB-induced apoptosis via the mitochondrial cell death pathway in melanoma cells.     

Distinct isocomplexes of the TRAPP trafficking factor coexist inside human cells

The transport protein particle (TRAPP) complex is required for proper vesicular transport from the ER to the Golgi. The composition of yeast TRAPP is well characterized, but the organization of mammalian TRAPP complex remains elusive. Using a tandem affinity purification (TAP) approach, we provide first experimental proof for the association of NIBP (NIK/IKKβ binding protein) with Bet3 and find two human paralogs of Trs33 (A and B) associated with Bet3. Interaction studies and gel filtration analysis reveal that both proteins are part of human TRAPP and might mark two distinct isocomplexes that exert different functions in the regulation of ER-to-Golgi traffic.

Structured summary

MINT-6784845:

Bet3 (uniprotkb:O43617) physically interacts (MI:0218) with Trs33B (uniprotkb:Q86SZ2) by anti bait coimmunoprecipitation (MI:0006)

MINT-6785053:

Trs33B (uniprotkb:Q86SZ2) physically interacts (MI:0218) with Bet3 (uniprotkb:O43617) and Sedl (uniprotkb:O14582) by anti bait coimmunoprecipitation (MI:0006)

MINT-6784856:

Bet3 (uniprotkb:O43617) physically interacts (MI:0218) with Trs33A2 (uniprotkb:O75865-2) by anti bait coimmunoprecipitation (MI:0006)

MINT-6785038:

Trs33A1 (uniprotkb:O75865-2) physically interacts (MI:0218) with Sedl (uniprotkb:O14582) and Bet3 (uniprotkb:O43617) by anti bait coimmunoprecipitation (MI:0006)

MINT-6784879:

Bet3 (uniprotkb:O43617) physically interacts (MI:0218) with NIBP (uniprotkb:Q96Q05) by tandem affinity purification (MI:0676)

MINT-6785068:

Trs33B (uniprotkb:Q86SZ2), Trs33A2 (uniprotkb:O75865-2) and Bet3 (uniprotkb:O43617) colocalize (MI:0403) by molecular sieving (MI:0071)

MINT-6785415:

Bet3 (uniprotkb:O43617) physically interacts (MI:0218) with Trs33A1 (uniprotkb:O75865) by anti bait coimmunoprecipitation (MI:0006)

     

血清IL-4、IL-6、IL-33与老年重症肺炎患者肠道菌群的相关性分析及对预后的影响

摘要 目的：探究老年重症肺炎患者血清白介素（IL）-4、IL-6、IL-33与肠道菌群变化的相关性及预后影响因素。方法：选取我院2020年1月-2022年1月期间收治的老年重症肺炎患者中筛选82例纳入重症组,从同期老年健康体检志愿者中选取50例纳入正常组。对比两组的IL-4、IL-6、IL-33与肠道菌群水平差异,Pearson相关系数分析肠道菌群与IL-4、IL-6、IL-33水平相关性,根据重症组随访6个月的预后情况分为生存组55例、死亡组27例,对比生存组、死亡组的临床因素差异,多因素Logistic回归模型分析重症肺炎死亡的影响因素。结果：（1）对比正常组,重症组的IL-4、IL-6、IL-33水平均明显升高（P<0.05）;（2）对比正常组,重症组的大肠埃希菌水平均明显升高且双歧杆菌水平明显降低（P<0.05）;（3）大肠埃希菌与IL-4、IL-6、IL-33均呈正相关,双歧杆菌与IL-4、IL-6、IL-33均呈负相关;（4）对比生存组,死亡组年龄、急性生理和慢性健康（APACHE-Ⅱ）评分、IL-4、IL-6、IL-33、大肠埃希菌、机械通气比例、餐后2 h平卧比例均明显更高且双歧杆菌明显更低（P<0.05）;（5）重症肺炎死亡的独立危险因素包括年龄增加、APACHE-Ⅱ评分升高、IL-4升高、IL-6升高、IL-33升高、大肠埃希菌升高、机械通气、餐后2 h平卧且独立保护因素是双歧杆菌升高。结论：老年重症肺炎患者存在明显的炎症反应与肠道菌群失衡,患者的IL-4、IL-6、IL-33、大肠埃希菌、双歧杆菌异常变化并且存在密切关系,老年重症肺炎患者的年龄、机械通气、餐后体位等因素均会影响其预后生存结局。     

血清IL-17、IL-32、IL-33、IL-37联合检测对初治多发性骨髓瘤患者早期治疗反应性的预测价值

摘要 目的：探讨血清白细胞介素-17（IL-17）、白细胞介素-32（IL-32）、白细胞介素-33（IL-33）、白细胞介素-37（IL-37）联合检测对接受硼替佐米为基础一线治疗方案的初治多发性骨髓瘤（MM）患者早期治疗反应性的预测价值。方法：选择2018年7月至2021年3月期间陕西省人民医院收治的初治MM患者176例为研究对象,所有患者均接受以硼替佐米为基础一线的治疗方案,根据早期治疗反应性分为敏感组（142例）和非敏感组（34例）;采用酶联免疫吸附法检测并比较两组血清IL-17、IL-32、IL-33、IL-37水平,并分析其联合检测对早期治疗反应性的预测价值。结果：敏感组治疗前血清IL-17、IL-32水平低于非敏感组,IL-33、IL-37水平高于非敏感组（P＜0.05）。多因素logistic回归分析显示,年龄≥65岁、血清IL-17≥29.70 pg/mL、IL-32≥63.02 ng/L、肿瘤分期III期是早期治疗反应性的危险因素（P＜0.05）,IL-33＞141.97 pg/mL、IL-37＞69.17 ng/L是保护因素（P＜0.05）。血清IL-17、IL-32、IL-33、IL-37联合检测预测早期治疗反应性的曲线下面积（AUC）为0.866（95%CI：0.801~0.972）。结论：年龄、肿瘤分期、血清IL-17、IL-32、IL-33、IL-37是MM患者早期治疗反应性的影响因素,联合检测血清IL-17、IL-32、IL-33、IL-37水平对接受硼替佐米为基础一线治疗方案的初治MM患者早期治疗反应性预测价值较高。     

Simultaneous radioimmunoassay of testosterone,dihydrotestosterone, 5α-androstane-3α, 17β-diol and 5α-androstane-3β, 17β-diol in the plasma of adult male rats

A single thin layer chromatography and three antibodies were used for the specific radioimmunoassay of four androgens in pooled rat plasma (Sprague-Dawley adult males). The following values were found (pg/ml ± SD). Testosterone : 3, 138 ± 173; dihydrotestosterone : 374 ± 20; 5α-androstane-3α 17β-diol : 284 ± 24; 5α-androstane-3β, 17β-diol : 223 ± 11.