Atypical Presentation of Testicular Adrenal Rest Tumor (TART) Leading to Bilateral Partial Orchiectomy in a 31-Year-Old Adult Revealing Primary Adrenal Insufficiency with CYP11A1 Deficiency

Adrenogenital syndrome is commonly associated with a deficiency in 21-hydroxylase but can be present in other rare enzymatic blocks. We report here the case of a 31-year-old man who presented with bilateral painful testicle lesions leading to bilateral partial orchiectomy as they were suspected for malignancy. These lesions were finally identified as benign testicle adrenal rest tumors (TARTs), and the patient was actually belatedly diagnosed with primary adrenal insufficiency due to 2 mutations of the CYP11A1 gene encoding the cholesterol side-chain cleavage enzyme (P450scc); the mutations were 940G > A (p.Glu314Lys) and c.1393C > T (p.Arg465Trp). The same mutations were found in his 29-year-old sister, who was then also diagnosed for primary adrenal insufficiency. Deficiency in P450scc is an extremely rare genetic autosomal recessive disorder with around 40 described families in the literature and 30 different mutations. As the diagnosis of delayed onset of P450Scc mutation is difficult, this case illustrates the need for a systematic endocrinological assessment in any case of bilateral testicle lesions, thus avoiding unnecessary surgery.

Preliminary Study on the Simulation of a Radiation Damage Analysis of Biodegradable Polymers

In this study, biodegradable poly(L-lactide-co-ε-caprolactone) (PLCL) and poly(L-co-d,l lactide) (PLDLA) were evaluated using Geant4 (G4EmStandardPhysics_option4) for damage simulation, in order to predict the safety of these biodegradable polymers against gamma ray sterilization. In the PLCL damage model, both chain scission and crosslinking reactions appear to occur at a radiation dose in the range 0–200 kGy, but the chain cleavage reaction is expected to be relatively dominant at high irradiation doses above 500 kGy. On the other hand, the PLDLA damage model predicted that the chain cleavage reaction would prevail at the total irradiation dose (25–500 kGy). To verify the simulation results, the physicochemical changes in the irradiated PLCL and PLDLA films were characterized by GPC (gel permeation chromatography), ATR-FTIR (attenuated total reflection Fourier transform infrared), and DSC (difference scanning calorimetry) analyses. The Geant4 simulation curve for the radiation-induced damage to the molecular weight was consistent with the experimentally obtained results. These results imply that the pre-simulation study can be useful for predicting the optimal irradiation dose and ensuring material safety, particularly for implanted biodegradable materials in radiation processing.

Non-Specific GH30_7 Endo-β-1,4-xylanase from Talaromyces leycettanus

This study describes the catalytic properties of a GH30_7 xylanase produced by the fungus Talaromyces leycettanus. The enzyme is an ando-β-1,4-xylanase, showing similar specific activity towards glucuronoxylan, arabinoxylan, and rhodymenan (linear β-1,3-β-1,4-xylan). The heteroxylans are hydrolyzed to a mixture of linear as well as branched β-1,4-xylooligosaccharides that are shorter than the products generated by GH10 and GH11 xylanases. In the rhodymenan hydrolyzate, the linear β-1,4-xylooligosaccharides are accompanied with a series of mixed linkage homologues. Initial hydrolysis of glucuronoxylan resembles the action of other GH30_7 and GH30_8 glucuronoxylanases, resulting in a series of aldouronic acids of a general formula MeGlcA2Xyln. Due to the significant non-specific endoxylanase activity of the enzyme, these acidic products are further attacked in the unbranched regions, finally yielding MeGlcA2Xyl2-3. The accommodation of a substituted xylosyl residue in the −2 subsite also applies in arabinoxylan depolymerization. Moreover, the xylose residue may be arabinosylated at both positions 2 and 3, without negatively affecting the main chain cleavage. The catalytic properties of the enzyme, particularly the great tolerance of the side-chain substituents, make the enzyme attractive for biotechnological applications. The enzyme is also another example of extraordinarily great catalytic diversity among eukaryotic GH30_7 xylanases.

EFFECT OF EMULSION SBR PREPARED BY ASYMMETRIC REVERSIBLE ADDITION-FRAGMENTATION TRANSFER AGENT ON PROPERTIES OF SILICA-FILLED COMPOUNDS

ABSTRACT The development of ultra-high-performance tires that satisfy fuel efficiency, traction, handling performance, and abrasion resistance has gained significant importance in the tire industry. Solution SBR has been used as a raw material, owing to its useful characteristics (e.g., narrow dispersity controllable microstructure and chain-end functionalization). In a recent improvement, emulsion SBR (ESBR), a high-molecular-weight compound with narrow dispersity, has been reported for application in the tire tread compounds. In particular, S,S-dibenzyl trithiocarbonate (DBTC) reversible addition-fragmentation transfer (RAFT) ESBR has exhibited excellent abrasion resistance and fuel efficiency in unfilled and carbon black–filled vulcanizates. However, owing to the symmetrical structure of DBTC RAFT ESBR, the polymer chain was shortened by the reaction of a silane coupling agent with trithiocarbonate, leading to poor abrasion resistance and fuel efficiency in the case of silica-filled vulcanizates. In this study, benzyl (4-methoxyphenyl) trithiocarbonate (BMPTC), an asymmetric RAFT agent that promotes unilateral polymer growth, was synthesized and used in the polymerization of BMPTC RAFT ESBR. Chain cleavage was not observed. Upon application to silica-filled vulcanizates, BMPTC RAFT ESBR exhibited improved abrasion resistance (by 9%), improved fuel efficiency (by 20%), and improved wet traction performance (by 10%) compared with the DBTC RAFT ESBR.

Hydrolytic stability of polyetherimide investigated in ultrathin films

Increasing the surface hydrophilicity of polyetherimide (PEI) through partial hydrolysis of the imide groups while maintaining the length of the main-chain was explored for adjusting its function in biomedical and membrane applications. The outcome of the polymer analogous reaction, i.e., the degree of ring opening and chain cleavage, is difficult to address in bulk and microstructured systems, as these changes only occur at the interface. Here, the reaction was studied at the air–water interface using the Langmuir technique, assisted by atomic force microscopy and vibrational spectroscopy. Slow PEI hydrolysis sets in at pH > 12. At pH = 14, the ring opening is nearly instantaneous. Reduction of the layer viscosity with time at pH = 14 suggested moderate chain cleavage. No hydrolysis was observed at pH = 1. Hydrolyzed PEI films had a much more cohesive structure, suggesting that the nanoporous morphology of PEI can be tuned via hydrolysis. Graphic abstract

Congenital Adrenal Hyperplasias Presenting in the Newborn and Young Infant

Congenital adrenal hyperplasia includes autosomal recessive conditions that affect the adrenal cortex steroidogenic enzymes (cholesterol side-chain cleavage enzyme; 3β-hydroxysteroid dehydrogenase; 17α-hydroxylase/17,20 lyase; P450 oxidoreductase; 21-hydroxylase; and 11β-hydroxylase) and proteins (steroidogenic acute regulatory protein). These are located within the three major pathways of the steroidogenic apparatus involved in the production of mineralocorticoids, glucocorticoids, and androgens. Many countries have introduced newborn screening program (NSP) based on 17-OH-progesterone (17-OHP) immunoassays on dried blood spots, which enable faster diagnosis and treatment of the most severe forms of 21-hydroxylase deficiency (21-OHD). However, in several others, the use of this diagnostic tool has not yet been implemented and clinical diagnosis remains challenging, especially for males. Furthermore, less severe classic forms of 21-OHD and other rarer types of CAHs are not identified by NSP. The aim of this mini review is to highlight both the main clinical characteristics and therapeutic options of these conditions, which may be useful for a differential diagnosis in the neonatal period, while contributing to the biochemical evolution taking place in the steroidogenic field. Currently, chromatographic techniques coupled with tandem mass spectrometry are gaining attention due to an increase in the reliability of the test results of NPS for detecting 21-OHD. Furthermore, the possibility of identifying CAH patients that are not affected by 21-OHD but presenting elevated levels of 17-OHP by NSP and the opportunity to include the recently investigated 11-oxygenated androgens in the steroid profiles are promising tools for a more precise diagnosis and monitoring of some of these conditions.

Improved Photocleavable Proteins with Faster and More Efficient Dissociation

The photocleavable protein (PhoCl) is a green-to-red photoconvertible fluorescent protein that, when illuminated with violet light, undergoes main chain cleavage followed by spontaneous dissociation of the resulting fragments. The first generation PhoCl (PhoCl1) exhibited a relative slow rate of dissociation, potentially limiting its utilities for optogenetic control of cell physiology. In this work, we report the X-ray crystal structures of the PhoCl1 green state, red state, and cleaved empty barrel. Using structure-guided engineering and directed evolution, we have developed PhoCl2c with higher contrast ratio and PhoCl2f with faster dissociation. We characterized the performance of these new variants as purified proteins and expressed in cultured cells. Our results demonstrate that PhoCl2 variants exhibit faster and more efficient dissociation, which should enable improved optogenetic manipulations of protein localization and protein-protein interactions in living cells.

In Search of New Therapeutics—Molecular Aspects of the PCOS Pathophysiology: Genetics, Hormones, Metabolism and Beyond

In a healthy female reproductive system, a subtle hormonal and metabolic dance leads to repetitive cyclic changes in the ovaries and uterus, which make an effective ovulation and potential implantation of an embryo possible. However, that is not so in the case of polycystic ovary syndrome (PCOS), in which case the central mechanism responsible for entraining hormonal and metabolic rhythms during the menstrual cycle is notably disrupted. In this review we provide a detailed description of the possible scenario of PCOS pathogenesis. We begin from the analysis of how a set of genetic disorders related to PCOS leads to particular malfunctions at a molecular level (e.g., increased enzyme activities of cytochrome P450 (CYP) type 17A1 (17α-hydroxylase), 3β-HSD type II and CYP type 11A1 (side-chain cleavage enzyme) in theca cells, or changes in the expression of aquaporins in granulosa cells) and discuss further cellular- and tissue-level consequences (e.g., anovulation, elevated levels of the advanced glycation end products in ovaries), which in turn lead to the observed subsequent systemic symptoms. Since gene-editing therapy is currently out of reach, herein special emphasis is placed on discussing what kinds of drug targets and which potentially active substances seem promising for an effective medication, acting on the primary causes of PCOS on a molecular level.