CASP microdomain formation requires cross cell wall stabilization of domains and non-cell autonomous action of LOTR1

Efficient uptake of nutrients in both animal and plant cells requires tissue-spanning diffusion barriers separating inner tissues from the outer lumen/soil. However, we poorly understand how such contiguous three-dimensional superstructures are formed in plants. Here, we show that correct establishment of the plant Casparian Strip (CS) network relies on local neighbor communication. We show that positioning of Casparian Strip membrane domains (CSDs) is tightly coordinated between neighbors in wild-type and that restriction of domain formation involves the putative extracellular protease LOTR1. Impaired domain restriction in lotr1 leads to fully functional CSDs at ectopic positions, forming 'half strips'. LOTR1 action in the endodermis requires its expression in the stele. LOTR1 endodermal expression cannot complement, while cortex expression causes a dominant-negative phenotype. Our findings establish LOTR1 as a crucial player in CSD positioning acting in a directional, non-cell-autonomous manner to restrict and coordinate CS positioning.

Pregnancy-associated breast cancer: the influence of gestational age

Whether PABC tumors arise before or during pregnancy and whether histopathology is affected by gestational age is currently unclear. The present study assesses the influence of gestational age and lactation on the histopathologic profile of PABC. We identified 744 patients with PABC (defined as breast cancer during pregnancy or 6-months following delivery). Histopathologic features were compared between pregnant and postpartum patients. Median age at diagnosis was 34.2 years and majority of cancers were diagnosed during pregnancy (71.3%). Within pregnant patients, tumors were significantly more often ER-negative in second and third trimesters (57.4%), as compared to first trimesters (41.9%) (p=0.036). Similarly, a PR-negative status was reported significantly less often within first trimesters (38.0%) compared to second and third trimesters (57.1%) (p=0.032). For HER2 status no significant differences were observed between gestational trimesters or lactating versus non-lactating patients. In postpartum patients, grade III tumors were found in over 80%, with high percentages of ER-negative tumors reaching 63% in those lactating versus 49% in non-lactating patients. This study demonstrates the varying histopathologic profile of PABC by gestational age and lactation status. Second and third trimester cancers display most typically the common ER/PR-negative phenotype, which is commonly reported in literature. The increased ER-negative status and percentage grade III tumors in lactating versus non-lactating patients also suggest presence of additional factors further diversify histology. This indicates the need for clear definitions of PABC and the role of potential subgroups, which may provide a stepping stone for further in-depth research into PABC-carcinogenesis.

FOXC1

Context.— Few studies have investigated the features of FOXC1 protein expression in invasive breast cancer subtypes as defined by immunohistochemistry (IHC)–based surrogate molecular classification. Objective.— To investigate the diagnostic utility of the IHC-based FOXC1 test in breast cancer subtyping and to evaluate the correlation between FOXC1 expression and clinicopathologic parameters in triple-negative breast cancer (TNBC). Design.— FOXC1 expression was evaluated with IHC in a large cohort of 2443 patients with breast cancer. Receiver operating characteristic (ROC) curves were used to assess the diagnostic ability of FOXC1 expression to predict the triple-negative phenotype and to identify the best cutoff value. FOXC1 expression was correlated with the clinicopathologic parameters of TNBC. Results.— The expression rate of FOXC1 in TNBC was significantly higher than in other subtypes. The area under the ROC curve confirmed the high diagnostic value of FOXC1 for the prediction of the triple-negative phenotype. The cutoff value of 1% showed a maximized sum of sensitivity and specificity. In TNBC, FOXC1 expression was significantly associated with aggressive tumor phenotypes. Furthermore, FOXC1 expression was primarily observed in invasive breast carcinoma of no special type and metaplastic carcinoma but rarely in invasive carcinoma with apocrine differentiation. Correspondingly, FOXC1 expression was significantly associated with the expression of basal markers but was negatively correlated with apocrine-related markers in TNBC. Conclusions.— In conclusion, FOXC1 is a highly specific marker for the triple-negative phenotype. Moreover, immunohistochemical detection of FOXC1 expression can be used as an additional diagnostic tool for the triple-negative phenotype and subclassification in TNBC.

The importance of being heterozygote: effects of RHD-genotype-sex interaction on the physical and mental health of a non-clinical population

Human populations, especially European, are polymorphic in the RHD gene. A significant fraction of their members carry no copy of the coding section of RHD gene, which results in their Rh-negative blood type. Theoretically, this polymorphism should be unstable. Carriers of the less frequent allele are penalized by reduced fertility because of the immunization of RhD-negative mothers by their RhD-positive babies, which results in hemolytic disease of the fetus and newborn in their subsequent progeny. For about 90 years, some form of balancing selection has been suspected to sustain this polymorphism. Several recent studies showed that the RhD-positive heterozygotes express higher viability than both types of homozygotes. However, the genotype of subjects in these studies was estimated only by indirect methods. Here we compared the physical and mental health of 178 women and 86 men who were directly tested for their RHD genotype. The results showed that RhD-positive homozygotic women had worse and RhD-positive homozygotic men better physical health than RhD-negative homozygotes; the difference between RhD-negative homozygotes and heterozygotes was not significant. Our results confirmed that health of RhD-positive heterozygotes and homozygotes differ. Therefore, any result of the comparison of subjects with RhD-positive and RhD-negative phenotype depends on the heterozygote-to-homozygote ratio in the RhD-positive sample. It is, therefore, crucial to analyze the effects of RHD-genotypes, not phenotypes in future studies.

Prevalence of Lewis Blood Group Polymorphisms in Southern Thai Blood Donors

Objective: To determine the frequencies of five of the most common (59T>G, 202T>C, 314C>T, 508G>A and 1067T>G) single nucleotide polymorphisms (SNPs) of the FUT3 gene in Thai blood donors and examine their associations with the presence or absence of Lewis antigens on red blood cells.Material and Methods: A total of 364 donor specimens from Songklanagarind Hospital and Regional Blood Centre XII Songkhla, Thailand, were recruited for the study. Molecular analysis of each SNP was performed by polymerase chain reaction amplification with sequence-specific primers (PCR-SSP). The Lewis phenotype was investigated in 159 individuals using the standard hemagglutination test.Results: The frequencies of the SNPs were 32.0% (59T>G), 46.6% (202T>C), 21.7% (314C>T), 37.9% (508G>A), and 25.0% (1067T>A). The prevalences of the Lewis phenotype were 61.0% for Le(a-b+), 7.6% for Le(a+b-), 11.3% for Le(a+b+), and 20.1% for Le(a-b-). The Lewis-negative phenotype was significantly associated with homozygosity in 59T>G and 1067T>A (χ2 =49.873, and χ2 =44.520, respectively).Conclusion: Our findings suggest that le59,1067 is largely responsible for the Lewis-negative phenotype in our southern Thai population. Genetic variations in FUT3 polymorphisms may be used as molecular markers for ethnicity and to help understand the roles of the Lewis blood group in infections or clinical diseases.

DEL in China: the D antigen among serologic RhD-negative individuals

Background Providing RhD-negative red cell transfusions is a challenge in East Asia, represented by China, Korea, and Japan, where the frequency of RhD-negative is the lowest in the world. Findings Among 56 ethnic groups in China, the RhD-negative frequency in Han, the prevalent ethnicity, is 0.5% or less, similar to most other ethnic groups. The Uyghur ethnic group has the highest reported RhD-negative frequency of up to 4.7%, as compared to 13.9% in the US. However, an estimated 7.15 million RhD-negative people live in China. The RhD-negative phenotype typically results from a loss of the entire RHD gene, causing the lack of the RhD protein and D antigen. The DEL phenotype carries a low amount of the D antigen and types as RhD-negative in routine serology. The DEL prevalence in RhD-negative individuals averages 23.3% in the Han, 17% in the Hui and 2.4% in the Uyghur ethnicities. The Asian type DEL, also known as RHD*DEL1 and RHD:c.1227G > A allele, is by far the most prevalent among the 13 DEL alleles observed in China. Conclusion The purpose of this review is to summarize the data on DEL and to provide a basis for practical strategy decisions in managing patients and donors with DEL alleles in East Asia using molecular assays.

RHD Genotyping of Rh-Negative and Weak D Phenotype among Blood Donors in Southeast Iran

Background: The D antigen is a subset of Rh blood group antigens involved in the hemolytic disease of the newborn [HDFN] and hemolytic transfusion reaction [HTR]. The hybrid Rhesus box that was created after RH gene deletion, was known as a mechanism of the Rh-negative phenotype. Hybrid marker identification is used to confirm the deletion of the RHD gene and to determine zygosity. This study aims to detect this marker in Rh-negative and weak D phenotype blood donors of the southeast of Iran. Materials and Methods: The molecular analysis of the hybrid Rhesus box was performed on the 200 Rh-negative blood donors in Sistan and Baluchestan province, southeast Iran. The presence of alleles responsible for the D variants was assessed by DNA sequencing in 26 weak D phenotype donors. Results: Of the 200 Rh-negative blood samples, 198 samples were homozygous (99%), and two samples were heterozygous (1%). Heterozygous samples had RHD*01N.73 allele and the RHD*01N.18 allele. Of the 26 samples with weak D phenotype, 16 partial DLO (61%), 4 partial DBT1 (15.3%), 2 partial DV type 2 (7.7%), 1 weak D type 1, 1 weak D type 4.2.3, 1weak D type 105 and 1 RHD (S103P) (4%) were determined. Conclusion: Since RHD gene deletion is the main mechanism of the Rh-negativity in Sistan and Baluchestan provinces, a hybrid Rhesus box marker can be used in resolving RhD typing discrepancies by RHD genotyping methods.