Biology subjects

Karim, M. A.

Publications and source records attributed to Karim, M. A..

3 recordsLinked to original sources

bioRxiv2018

Profile of Molecular Subtypes of Breast Cancer Among Bangladeshi Women - Audit of Initial Experience

BackgroundReceptor status and molecular subtyping of breast cancer are crucial for patient management. We present here our initial experience on the status of different molecular subtypes and clinicopathological characteristics of invasive breast carcinomas in Bangladeshi population especially in Chittagong zone.\n\nMaterials and methodsA total of 59 histopathologically confirmed cases of invasive ductal carcinoma were selected for this study. Fifteen out of 59 cases were reported as HER2 equivalent and could not be categorized into any subtype because of the lack of availability of fluorescence in situ hybridization. The remaining 44 cases were distributed into different molecular subtypes and then the clinicopathological characteristics were compared for each molecular subtype.\n\nResultsAge ranges from 24-70 years with a mean age of 43.95 years. Most of the patients were in 41-50 years age group. Among the 44 cases, most common subtype was HER2/neu amplification (13 cases, 29.55%). Luminal A, luminal B and basal like subtypes were 11 (25%), 10 (22.73%) and 10 (22.73%) respectively. The mean tumor size was 3.46 cm and the highest mean tumor size was in basal-like subtype (4.01cm). Twenty five out of 59 cases (42.37%) showed axillary lymph node metastasis. Lowest axillary lymph node metastasis was found in luminal A subtype (3/11=27.27%).\n\nConclusionHER2/neu amplification subtype was found to be more common in this region. Luminal A subtype was found to be more favorable in comparison to the other subtypes in terms of axillary lymph node metastasis.

pathology↗

bioRxiv2017

The Na+(K+)/H+ exchanger Nhx1 controls multivesicular body-vacuolar lysosome fusion

Loss-of-function mutations in human endosomal Na+(K+)/H+ Exchangers (NHEs) NHE6 and NHE9 are implicated in neurological disorders including Christianson Syndrome, autism and attention deficit and hyperactivity disorder (ADHD). These mutations disrupt retention of surface receptors within neurons and glial cells by affecting their delivery to lysosomes for degradation. However, the molecular basis of how these endosomal NHEs control endocytic trafficking is unclear. Using Saccharomyces cerevisiae as a model, we conducted cell-free organelle fusion assays to show that transport activity of the orthologous endosomal NHE Nhx1 is important for multivesicular body (MVB)-vacuolar lysosome fusion, the last step of endocytosis required for surface protein degradation. We find that deleting Nhx1 disrupts the fusogenicity of the MVB, not vacuole, by targeting pH-sensitive machinery downstream of the Rab-GTPase Ypt7 needed for SNARE-mediated lipid bilayer merger. All contributing mechanisms are evolutionarily conserved offering new insight into the etiology of human disorders linked to loss of endosomal NHE function.

cell biology↗

bioRxiv2017

Distinct features of multivesicular body-lysosome fusion revealed by a new cell-free content-mixing assay

When marked for degradation, surface receptor and transporter proteins are internalized and delivered to endosomes where they are packaged into intralumenal vesicles (ILVs). Many rounds of ILV formation create multivesicular bodies (MVBs) that fuse with lysosomes exposing ILVs to hydrolases for catabolism. Despite being critical for protein degradation, the molecular underpinnings of MVB-lysosome fusion remain unclear, although machinery underlying other lysosome fusion events is implicated. But how then is specificity conferred? And how is MVB maturation and fusion coordinated for efficient protein degradation? To address these questions, we developed a cell-free MVB-lysosome fusion assay using S. cerevisiae as a model. After confirming that the Rab7 ortholog Ypt7 and the multisubunit tethering complex HOPS are required, we found that the Qa-SNARE Pep12 distinguishes this event from homotypic lysosome fusion. Mutations that impair MVB maturation block fusion by preventing Ypt7 activation, confirming that a Rab-cascade mechanism harmonizes MVB maturation with lysosome fusion.\n\nIMPACT STATEMENTEndocytosis culminates with multivesicular bodies (MVBs) fusing with lysosomes. But the molecular underpinnings of this event remain unclear. Here, using S. cerevisiae as a model, Karim et al. employ a new in vitro assay to show that MVB-lysosome fusion is driven by ESCRT-dependent Rab-GTPase activation and the syntaxin ortholog Pep12, distinguishing it from other lysosome membrane fusion events.

cell biology↗