Case report of whole genome sequencing in the XY female: identification of a novel <Emphasis Type="Italic">SRY</Emphasis> mutation and revision of a misdiagnosis of androgen insensitivity syndrome

Background

The 46,XY female is characterised by a male karyotype and female phenotype arising due to any interruption in the sexual development pathways in utero. The cause is usually genetic and various genes are implicated.

Case presentation

Herein we describe a 46,XY woman who was first diagnosed with androgen insensitivity syndrome (testicular feminisation) at 18 years; however, this was later questioned due to the presence of intact Müllerian structures. The clinical phenotype suggested several susceptibility genes including SRY, DHH, NR5A1, NR0B1, AR, AMH, and AMHR2. To study candidate genes simultaneously, we performed whole genome sequencing. This revealed a novel and likely pathogenic missense variant (p.Arg130Pro, c.389G>C) in SRY, one of the major genes implicated in complete gonadal dysgenesis, hence securing this condition over androgen insensitivity syndrome as the cause of the patient’s disorder of sexual development.

Conclusion

This case highlights the emerging clinical utility of whole genome sequencing as a tool in differentiating disorders of sexual development.

     

Marginal zone lymphoma-derived interfollicular diffuse large B-cell lymphoma harboring 20q12 chromosomal deletion and missense mutation of <Emphasis Type="Italic">BIRC3</Emphasis> gene: a case report

Background

Diffuse large B-cell lymphoma (DLBCL) typically leads to effacement of the nodal architecture by an infiltrate of malignant cells. Rarely (<1%), DLBCL can present with an interfollicular pattern (DLBCL-IF) preserving the lymphoid follicles. It has been postulated that DLBCL-IF is derived from marginal zone B cells and may represent a large-cell transformation of marginal zone lymphoma (MZL), however no direct evidence has been provided to date. Here we describe a rare case of a diagnostically challenging DLBCL-IF involving a lymph node in a patient with a prior history of lymphadenopathy for several years and MZL involving skin.

Case presentation

A 53-year old man presented to our Dermatology Clinic due to a 1-year history of generalized itching, fatigue of 2–3 month’s duration, nausea and mid back rash that was biopsied. PET (positron emission tomography)/CT (computed tomography) was performed and revealed inguinal, pelvic, retroperitoneal, axillary, and cervical lymphadenopathy. The patient was referred to surgery for excisional biopsy of a right inguinal lymph node.Diagnostic H&E stained slides and ancillary studies were reviewed for the lymph node and skin specimens. B-cell clonality by PCR and sequencing studies were performed on both specimens.We demonstrate that this patient’s MZL and DLBCL-IF are clonally related, strongly suggesting that transformation of MZL to DLBCL had occurred. Furthermore, we identified a novel deletion of the long arm of chromosome 20 (del(20q12)) and a missense mutation in BIRC3 (Baculoviral IAP repeat-containing protein 3) in this patient’s DLBCL that are absent from his MZL, suggesting that these genetic alterations contributed to the large cell transformation.

Conclusions

To our knowledge, this is the first report providing molecular evidence for a previously suspected link between MZL and DLBCL-IF. In addition, we describe for the first time del(20q12) and a missense mutation in BIRC3 in DLBCL. Our findings also raise awareness of DLBCL-IF and discuss the diagnostic pitfalls of this rare entity.

     

Solvation structure of sodium chloride (Na+–Cl-) ion pair in acetonitrile (AN)–dimethyl formamide (DMF) mixtures

Solvation structures of Na⁺–Cl^? ion pair are investigated in acetonitrile (AN)–dimethylformamide (DMF) isodielectric mixtures. The potentials of mean force of Na⁺–Cl^? in the five compositions of mixtures show minima corresponding to a contact ion pair (CIP) and a solvent-shared ion pair (SShIP). The solvent-separated ion pair minima are present in lower mole fractions of AN (x_AN ≤ 0.50). CIPs are found to be more stable than the SShIPs. From a thermodynamic decomposition of the potentials of mean force, we find that the formation of the ion pair is entropically driven in these compositions. The most stable CIP is in pure AN. The local solvation structures around the ion pair are analysed through the running coordination numbers, excess coordination numbers, solvent orientational distributions and density profiles. We find that both Na⁺ and Cl^? are preferentially solvated by DMF.     

Microalga Scenedesmus bajacalifornicus BBKLP-07, a new source of bioactive compounds with in vitro pharmacological applications

Microalgae are photosynthetic eukaryotes which are primary producers in the food chain and also excellent sources for bioactive compounds such as alkaloids, flavonoids, phenols, saponins and other fine chemicals. In the present study, the microalga Scenedesmus bajacalifornicus BBKLP-07 was subjected to soxhlet extraction using solvents like chloroform, acetone, ethanol, methanol and aqueous solvents. All the solvents were tested for the presence of phytochemical constituents such as alkaloids, flavonoids, glycosides, phenols, lignin’s, saponins, sterols, tannins, anthraquinone and reducing sugar using the standard procedures. Furthermore, all the crude extracts were subjected to antidiabetic, antioxidant, anti-inflammatory and antimicrobial activities. Antidiabetic activity of the microalgal extracts was observed maximum in Aqueous extract. Methanolic extracts have shown maximum antioxidant activity and chloroform extracts have exhibited highest anti-inflammatory effects. Antimicrobial activities were tested against E.coli, S, typhi, C.perfringens and B.subtilis bacteria and fungi A.niger, and C. albicans. Therefore, the green microalga Scenedesmus bajacalifornicus BBKLP-07 is a rich source of biological active compounds and nutraceuticals and can be exploited for commercial applications.

     

Biosurfactant production: emerging trends and promising strategies

Biosurfactants are economically most sought after biotechnological compounds of the 21st century. However, inefficient bioprocessing has mitigated the economical commercial production of these compounds. Although much work is being done on the use of low-cost substrates for their production, a paucity of literature exists on the upcoming bioprocess optimization strategies and their successes and potential for economical biosurfactant production. This review discusses some of the latest developments and most promising strategies to enhance and economize the biosurfactant production process. Recent market analysis, developments in the field of optimally formulated cost credit substrates for enhanced product formation and subsequent process economization are few of the critical aspects highlighted here. Use of nanoparticles and coproduction of biosurfactant along with other commercially important compounds like enzymes, are other upcoming bioprocess intensification strategies. The recent developments discussed here would not only give an overview of pertinent parameters for economic biosurfactant production but would also bring to fore multiple strategies that would open up new avenues of research on biosurfactant production. This would go a long way in making biosurfactants a commercially successful compound of the current century.     

Validated Postbiotic Screening Confirms Presence of Physiologically-Active Metabolites,Such as Short-Chain Fatty Acids,Amino Acids and Vitamins in Hylak® Forte

Probiotics and Antimicrobial Proteins - Hylak® forte is a postbiotic that inhibits the growth of pathogenic bacteria by reducing intestinal pH. It is assumed the potential presence of...     

Study of the Geometry and Folding Pattern of Leaves of Mimosa pudica

Many structural and functional properties possessed by plants have great potentials to stimulate new concepts and inno-vative ideas in the field of biomimetic engineering. The key inputs from biology can be used for creation of efficient and op-timized structures. The study of the geometry and folding pattern of leaves of Mimosa pudica,referred as Sensitive Plant,reveals some of the peculiar characteristics during folding and unfolding. When the leaf is touched,it quickly folds its leaflets and pinnae and droops downward at the petiole attachment. With the help of experiments on simulation model,the variations in angle of leaflets and degree of compaction after folding are investigated.     

An improved HPLC method for the analysis of citrus limonoids in culture media

Recent studies have shown that citrus limonoids have potential health benefits. However, information on the absorption and metabolism of limonoids in human gastrointestinal (GI) tract is limited. In the present study we have investigated the metabolism of limonin glucoside (LG), the predominant limonoid in citrus by four microorganisms (Enterococcus fecalis, Escherichia coli, Lactobacillus salivarius, and Candida albican) widely present in the human lower GI tract. LG and metabolites in the culture medium were purified using solid phase extraction and analyzed using HPLC using UV detection at 210nm. The identity of LG was further confirmed by electrospray ionization mass spectrometry (ESI-MS). Significant metabolic activity of Escherichia coli and Candida albican on LG was observed. Several unidentified metabolites were also found in the medium. The results of the present study indicated that LG may be metabolized in the intestine by some microbes. Further studies are needed to establish the possible route of LG metabolism in the human system.