Linkers: A synergistic way for the synthesis of chimeric proteins.

In the cell, the protein domains are attached with the short oligopeptide, commonly known as linker peptide. Besides bridging, the linker assists in the domain-domain interaction and protein folding into the peculiar conformations. Linkers allow or control the movement of protein domains in the dynamic cellular environment. The recent advances in the recombinant DNA technology enable the construction of multiple gene constructs in an open reading frame. The express sequences can work in a cascade to cater for myriad functions. This trend has given momentum to incorporating bridge sequences (linker) that essentially separates the independent domains. According to the cellular need, the bridging partner can be spaced at a secure gap or requires attaching or interacting physically. The flexible or rigid linker can help to achieve such conformations in chimeric fusion proteins. The linker can improve solubility, proteolytic resistance and stability of such fusion proteins. Recently, linker aided protein switches and antibody-drug conjugates are gaining the attention of researchers worldwide. Here, we thoroughly reviewed the types of the linker, strategies for linker engineering and the composition of a linker.

The road less travelled: The efficacy of canine pluripotent stem cells.

The path-breaking discovery of induced pluripotent stem cells has fuelled the scientific advancements of stem cells. Nevertheless, the need to ensure the safety of stem cell therapy at translational level is still at large, prompting scientists to use animal models which are genetically and anatomically homologous to that of humans. Dogs, being genomically and physiologically more similar to humans serve as better models in mimicking human diseases as compared to rodents. The heterogeneity in canine breeds offers an excellent opportunity to comprehend the complexities of many genetic diseases, making them exceptional tools for stem cell therapies. Various canine gene therapy models have paved the foundation for strategizing therapies for humans. But a similar progress is lacking in utilizing canine stem cells for stem cell-based therapies in both dogs and humans. This review attempts to bridge the gap, by articulating the key differences in canine pluripotency pathways, based on the recent derivation of canine embryonic stem cells (cESCs) and canine induced pluripotent stem cells (ciPSCs), thereby attempting to position dog in the reprogramming landscape. The potential clinical application of canine iPSCs also offers great hope to canine patients and might lead to significant contributions in veterinary medicine.

Feature-driven classification reveals potential comorbid subtypes within childhood apraxia of speech.

BACKGROUND: Childhood apraxia of speech (CAS) is a neurodevelopmental disorder with heterogeneous communication and other comorbid manifestations. While previous studies have characterized speech deficits associated with CAS, few studies have examined variability in reading and language and/or other developmental comorbidities. We sought to identify comorbid subgroups within CAS that could be clinically relevant as well as genetically distinctive. METHODS: In a group of 31 children with CAS and 8 controls, we performed hierarchical cluster analysis utilizing measures of articulation, vocabulary, and reading. We also conducted a chart review of the children with CAS to examine other clinical characteristics in these children and their association with subgroup membership. RESULTS: We identified 3 comorbid subgroups within CAS of varying severity. The high severity subgroup was characterized by poor reading and vocabulary, and the moderate severity subgroup by poor reading and non-word repetition but average vocabulary, compared to the mild severity subgroup. Subgroups were indistinguishable with respect to speech sound production, the hallmark of CAS, all demonstrating poor articulation. Children in the most severe subgroup were more likely to have early problems feeding (p = 0.036). CONCLUSIONS: Children with CAS may potentially be classified into comorbidity groups based on performance on vocabulary and reading measures, providing additional insight into the heterogeneity within CAS with implications for educational interventions.

A Rare Case Report of Dedifferentiated Endometrioid Carcinoma.

Dedifferentiated endometrioid carcinoma (DEC) is an exceptionally rare subtype of endometrial cancer characterized by a high-grade component juxtaposed with a low-grade endometrioid adenocarcinoma. This case report presents a unique instance of dedifferentiated endometrioid carcinoma in a 64-year-old female patient who presented with post-menopausal bleeding and abdominal pain. Diagnostic evaluation including imaging studies and histopathological examination revealed a mixed tumor comprising both high-grade and low-grade components. Management involved a multidisciplinary approach including surgical resection followed by adjuvant chemotherapy and radiation therapy. They are frequently mislabeled as endometrioid carcinomas of International Federation of Gynecology and Obstetrics (FIGO) Grade 2 or Grade 3. It is crucial to correctly differentiate these instances from traditional endometrioid carcinomas. This case underscores the importance of early recognition and comprehensive management strategies tailored to the unique characteristics of dedifferentiated endometrioid carcinoma. We report this case due to its rarity and complexity in diagnosis.

Positioning canine induced pluripotent stem cells (iPSCs) in the reprogramming landscape of naïve or primed state in comparison to mouse and human iPSCs.

AIMS: Deriving canine-induced pluripotent stem cells (ciPSCs) have paved the way for developing novel cell-based disease models and transplantation therapies in the dog. Though ciPSCs have been derived in the presence of Leukemia inhibitory factor (LIF) as well in the presence of basic fibroblast growth factor (bFGF), the positioning of ciPSCs in the naïve or the primed state of pluripotency remains elusive. This study aims to understand whether canine iPSCs belong to naïve or prime state in comparison to mouse (m) iPSCs and human (h) iPSCs. MAIN METHODS: In the present study, we derived ciPSCs in presence of LIF and compared their state of pluripotency with that of miPSCs and hiPSCs by culturing them in the presence of LIF, bFGF, and LIF + bFGF. Gene expression level at transcript level was performed by RT-PCR and qRT-PCR and at the protein level was analysed by immunofluorescence. We also attempted to understand the pluripotency state using lipid body analysis by bodipy staining and blue fluorescence emission. KEY FINDINGS: In contrast to miPSCs, the naïve pluripotent stem cells, ciPSCs showed the expression of FGF5 similar to that of primed pluripotent stem cell, hiPSCs. Compared to miPSCs, ciPSCs cultured in presence of LIF showed enhanced expression of primed pluripotent marker FGF5, similar to hiPSCs cultured in presence of bFGF. Upon culturing in hiPSC culture condition, ciPSCs showed enhanced expression of core pluripotency genes compared to miPSCs cultured in similar condition. However, ciPSCs expressed naïve pluripotent marker SSEA1 similar to miPSCs and lacked the expression of primed state marker SSEA4 unlike hiPSCs. Interestingly, for the first time, we demonstrate the ciPSC pluripotency using lipid body analysis wherein ciPSCs showed enhanced bodipy staining and blue fluorescence emission, reflecting the primed state of pluripotency. ciPSCs expressed higher levels of fatty acid synthase (FASN), the enzyme involved in the synthesis of palmitate, similar to that of hiPSCs and higher than that of miPSCs. As ciPSCs exhibit characteristic properties of both naïve and primed pluripotent state, it probably represents a unique intermediary state of pluripotency that is distinct from that of mice and human pluripotent stem cells. SIGNIFICANCE: Elucidating the pluripotent state of ciPSCs assists in better understanding of the reprogramming events and development in different species. The study would provide a footprint of species-specific differences involved in reprogramming and the potential implication of iPSCs as a tool to analyse evolution.

Epithelioid angiomyolipoma of liver with an inflammatory component: a case report.

Angiomyolipomas (AMLs) are benign mesenchymal tumors seen in kidneys in association with tuberous sclerosis. They are uncommon in liver. Angiomyolipomas of liver show great histological diversity and various types and patterns are described. Among them, epithelioid and inflammatory angiomyolipomas are rare. We report a case of epithelioid angiomyolipoma of Liver with an inflammatory component.