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Copyright of Minufiya Journal of Agricultural Research is the property of Egyptian National Agricultural Library (ENAL) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Hybrids have been obtained by protoplast fusion of nitrate-non-utilizing cnx- and acetate-nonutilizing fac-mutants of Penicillium chrysogenum strains 4/95 and 26/818, respectively. Induced haplodization of the hybrids allowed the recovery of stable segregants, which were screened for penicillin production. The penicillin-producing segregants showed a wide range of titers that reached for a certain mutant to 290-390% increase above the parent strains. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Ernäehrungswissenschaft is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: The purpose of this study is to show the preliminary results of using chitosan-based scaffold (BST-CarGel®) with microfracture for treatment of acetabular chondral delamination associated with femoroacetabular impingement. Methods: A prospective study was performed on 13 hips. Patients were selected in the age group between 18 and 50 years. Patients with delamination of acetabular cartilage associated with femoroacetabular impingement received arthroscopic debridement and microfracture technique. Then cases with defect > 2 cm2 were considered for the application of BST-CarGel® and included in the study. Also, reattachment of the torn labrum and resection of the cam deformity were performed according to the case. For evaluation of the functional outcome, the patients had completed the hip outcome score (HOS) pre- and post-operatively. For evaluation of the regeneration of the cartilage, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) was used and the percentage of defect filling and type of cartilage studied. Results: Patients had a mean age of 41 years, with moderate to high level of activity (mean Tegner scale 7). The mean size of the chondral defect after debridement was 3.7 cm2. The mean HOS for daily live activities has been improved from 64.4 to 87.4 and for sports subscale from 35.2 to 75.2, which is statistically highly significant. All patients had > 90% of filling of chondral defect. Conclusion: The use of BST-CarGel® with microfracture for treatment of acetabular chondral delamination associated with femoroacetabular impingement can improve the functional outcome at two years, with a complete restoration of the cartilage defect in magnetic resonance images (MRI) with specific cartilage sequences.

Introduction Tourniquets are vital devices in orthopaedic surgery that aid in creating a bloodless field. While they reduce operative time and outcomes, improper use can lead to severe complications. The British Orthopaedic Association Standards for Trauma (BOAST) offers guidelines for safe intraoperative tourniquet usage, emphasising proper application and accurate documentation. With the push for a paperless National Health Service (NHS), orthopaedic units across the UK are transitioning to electronic patient records (EPR). In this audit, we aim to evaluate the impact of electronic patient records (EPR) implementation on tourniquet documentation and subsequent interventions to enhance guideline adherence. Methods This closed-loop audit evaluated 159 emergency trauma cases at a single UK-based district general hospital across three different cycles. The first cycle (n=50) was collected before the trust-wide adoption of an EPR system (EPIC HIVE). Upon collecting the second cycle (n=59), local intraoperative tourniquet usage results compared to BOAST were presented at a departmental audit meeting. A specialised smart phrase template was subsequently shared with the department and the results were re-audited in the third cycle (n=50). Statistical analyses were performed to compare the cycles. Results Following the introduction of the EPR, compliance with documentation standards (fully and partially adhered to) initially declined from 38.0% to 17.0%. Post-intervention, compliance increased to 62.0% (p=0.0005). Individual aspects of documentation revealed notable improvements, including increases in skin assessment pre- and post-tourniquet application (0% to 56% and 0% to 60%, respectively, p<0.0001), isolation method (0% to 60%, p<0.0001), exsanguination method (2% to 24%, p=0.0003), tourniquet pressure (39% to 76%, p=0.0001) and tourniquet time (59% to 94%, p=0.0001). Lower limb tourniquet pressures significantly decreased between audit cycles (mean: 287.06 vs mean: 265.91, p=0.007) while upper limb pressures remained relatively stable (mean: 236.67 vs mean: 236.56, p=0.993). No tourniquet-related complications were reported across all audit cycles. Conclusion While the introduction of new EPR systems may initially present challenges in upholding accurate operative records, the incorporation of specialised electronic templates and active staff engagement has shown to be instrumental in improving tourniquet safety and enhancing care standards., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kafagi et al.)

Objective: The primary objective of this study is to assess the adherence of our department to the British Orthopaedic Association's Standards for Trauma and Orthopaedics (BOAST) guidelines for "the care of the older or frail orthopaedic trauma patient" and the results of this adherence on clinical patient outcome measures., Methods: This was a clinical audit. All ≥65-year-olds admitted to the orthopaedic department with a fragility fracture between 8 September 2022 and 8 March 2023 with a length of stay (LOS) of >72 hours were included. Patients were stratified into hip fracture (HF) and non-hip fracture (NHF) patients. A further similar cohort of NHF admissions between 8 March and 8 May 2023 was added to the data. The adherence of both cohorts to the national guidelines was recorded. Primary outcome measures of each cohort were recorded such as LOS and patient mortality., Results: Data from 70 patients was collected. HF patients adhered to the guideline 79.4% of the time (31/39 patients) compared to NHF patients at only 19.3% of the time (6/31 patients) (p<0.001). Further, on average, HF patients were seen by an orthogeriatrician 15 times compared to just five times for NHF patients during their hospital stay (p<0.001). No significant difference in LOS or in mortality at 30 days post-admission was observed., Conclusion: Medical orthogeriatric care is unequal despite similar LOS and mortality between both cohorts; thus, increasing orthogeriatrician input in NHF patients may lead to better patient outcomes for these patients., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tahoun et al.)

Background: The role of autophagy in coronaviruses infection and replication has a lot of debate. Autophagy involves the catalytic breakdown of intracellular components to be subsequently recycled by the lysosome. The aim of the study was to evaluate autophagy genes; PIK3C3 and RAB7A expressions in COVID-19 patients, and identify if PIK3C3 and RAB7A can be used as markers for monitoring COVID-19 patients., Methods: A case-control study was carried out on 50 patients and 50 healthy controls. Genes expression was performed using quantitative real-time polymerase chain reaction., Results: Compared to controls, PIK3C3 and RAB7A gene expression levels were significantly lower in patients (p < 0.001) with approximately with 9.4 and 2.3 decreased fold in PIK3C3 and RAB7A respectively. The ROC curve of PIK3C3 and RAB7A expressions showed sensitivity of 84 % and 74 % and specificity of 98 % and 78 % respectively. There was a positive correlation between PIK3C3 expression and WBCs, absolute neutrophil count, interleukin-6, D-dimer, and ALT among patients and between RAB7A expression and WBCs, CRP, IL-6, D-dimer and ALT in patients., Conclusions: The study showed reduction of PIK3C3 and RAB7A expressions in COVID-19 patients. However, further studies are recommended to clarify their roles in the disease pathogenies as autophagy genes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Suberin, a complex biopolymer, forms a water- and gas-insoluble barrier that protects the inner tissues of plants. It is abundant in tree bark, particularly in the cork oak Quercus suber. Anatomically, fossil bark has been described since the Devonian. However, its distinctive constituent suberin has not yet been reported from the fossil record. Here we present unambiguous chemical evidence for intact suberin from the bark of a middle Eocene monkeyhair tree from Geiseltal, eastern Germany. High-performance liquid chromatography coupled to electrospray ionization mass spectrometry (HPLC-ESI-MS) detected constituents of suberin in the outer layer the fossil monkeyhair tree, which confirms previous morphological interpretation of this tissue as bark, and chemically differentiates this layer from the two tissues of the inner layer. Notably, this is the first study with compelling chemical evidence for suberin in fossil bark. Fluorescence microspectroscopy additionally supports the presence of suberin. Fossilization conditions in the Eocene Geiseltal deposit were likely mild, with low moisture and temperatures, contributing to the remarkable preservation of bark and inner laticifer mats of the monkeyhair trees growing there 45 million years ago., (© 2024. The Author(s).)

Treating estrogen-dependent diseases like endometriosis with drugs suppressing local estrogen activation may be superior to existing endocrine therapies. Steroid sulfatase (STS) and 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) are key enzymes of local estrogen activation. We describe the rational design, synthesis, and biological profilation of furan-based compounds as a novel class of dual STS/17β-HSD1 inhibitors (DSHIs). In T47D cells, compound 5 showed irreversible inhibition of STS and potent, reversible inhibition of 17β-HSD1. It was selective over 17β-HSD2 and displayed high metabolic stabilities in human and mouse liver S9 fractions. No effect on cell viability was detected up to 31 μM (HEK293) and 23 μM (HepG2), respectively, and there was no activation of the aryl hydrocarbon receptor (AhR) up to 3.16 μM. Single daily application to mice revealed steady-state plasma levels high enough to make this compound eligible for an in vivo proof-of-principle study in a mouse endometriosis model.

The metalloporphyrin heme acts as the oxygen-complexing prosthetic group of hemoglobin in blood. Heme has been noted to survive for many millions of years in fossils. Here, we investigate its stability and degradation under various conditions expected to occur during fossilization. Oxidative, reductive, aerobic, and anaerobic conditions were studied at neutral and alkaline pH values. Elevated temperatures were applied to accelerate degradation. High-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) identified four main degradation products. The vinyl residues are oxidized to formyl and further to carboxylate groups. In the presence of air or H 2 O 2 , cleavage of the tetrapyrrole ring occurs, and hematinic acid is formed. The highest stability of heme was observed under anaerobic reductive conditions (half-life 9.5 days), while the lowest stability was found in the presence of H 2 O 2 (half-life 1 min). We confirmed that the iron cation plays a crucial role in degradation, since protoporphyrin IX, lacking iron, remained significantly more stable. Under anaerobic, reductive conditions, the above-mentioned degradation products were not observed, suggesting a different degradation pathway. To our knowledge, this is the first molecular taphonomy study on heme, which will be useful for understanding its fate during fossilization.

Aim of the Study: Identifying persons at increased risk of developing hepatocellular carcinoma (HCC) after exposure to directly acting antivirals (DAAs) is of utmost importance. Our aim was to identify the predictors of de novo HCC occurrence among cirrhotic patients after hepatitis C virus (HCV) treatment using DAAs., Material and Methods: 529 cirrhotic patients who initiated treatment for HCV using DAAs were followed up for 2 years from the end of treatment for development of HCC. Pretreatment clinical and laboratory data were assessed as possible predictors for HCC occurrence. Genotyping for tolloid-like 1 gene ( TLL1 ) variant rs17047200 was assessed in all patients who developed HCC and in the matched control group., Results: Pretreatment bilirubin, FIB-4 and platelet-albumin-bilirubin (PALBI) scores were significantly higher among those who developed HCC than those who did not develop HCC during the 2-year follow-up period while hemoglobin level was significantly lower. ROC curve analysis revealed that at a cut-off ≥ 3.07, pretreatment FIB-4 had a sensitivity of 76.5%, and negative predictive value (NPV) of 92%. At a cut-off ≥ -2.5, pretreatment PALBI score had a sensitivity of 82.4%, and NPV of 93.2%. Regarding genotyping for TLL1 rs17047200 there were no statistically significant differences between those who developed HCC during follow-up and the matched control group., Conclusions: TLL1 rs17047200 genotyping is not helpful in predicting HCC occurrence after DAAs. On the other hand, lower pretreatment hemoglobin level and higher pretreatment bilirubin, FIB-4 and PALBI scores are associated with higher risk of HCC development after DAAs., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Clinical and Experimental Hepatology.)

A novel approach for the dual inhibition of steroid sulfatase (STS) and 17β-hydroxysteroid dehydrogenase type 1(17β HSD1) by a single drug was explored, starting from in-house 17β HSD1 inhibitors via masking their phenolic OH group with a sulfamate ester. The sulfamates were intentionally designed as drugs for the inhibition of STS and, at the same time, prodrugs for 17β-HSD1 inhibition ("drug-prodrug approach"). The most promising sulfamates 13, 16, 18-20, 22-24, 36, and 37 showed nanomolar IC 50 values for STS inhibition in a cellular assay and their corresponding phenols displayed potent 17β-HSD1 inhibition in cell-free and cellular assays, high selectivity over 17β-HSD2, reasonable metabolic stability, and low estrogen receptor α affinity. A close relationship was found between the liberation of the phenolic compound by sulfamate hydrolysis and 17β-HSD1 inactivation. These results showed that the envisaged drug-prodrug concept was successfully implemented. The novel compounds constitute a promising class of therapeutics for the treatment of endometriosis and other estrogen-dependent diseases.

The preservation of soft tissue in the fossil record is mostly due to the replacement of organic structures by minerals (e.g. calcite, aragonite or apatite) called pseudomorphs. In rare cases soft tissues were preserved by pyrite. We assume that adipocere, as the shaping component, might be a preliminary stage in the pyritisation of soft tissues under anaerobic conditions. Using high-performance liquid chromatography coupled to ultraviolet and mass spectrometric detection (HPLC-UV/MS) and confocal Raman spectroscopy (CRS) we were able to demonstrate the transformation of the hepatopancreas (digestive gland) of the crayfish Cambarellus diminutus [Hobbs 1945] into adipocere within only 9 days, just inside a biofilm. Microorganisms (bacteria and fungi) which were responsible for the biofilm (Sphaerotilus [Kutzig 1833] and Pluteus [Fries 1857]) and maybe the adipocere formation (Clostridium [Prazmowski 1880]) were detected by 16S rRNA gene amplicon sequencing. Furthermore, micro-computed tomography (µ-CT) analyses revealed a precipitation of calcite and further showed that in animals with biofilm formation calcite precipitates in finer grained crystals than in individuals without biofilm formation, and that the precipitates were denser and replicated the structures of the cuticles better than the coarse precipitates., (© 2022. The Author(s).)

In April 2020, the Ministry of Health (MoH) in Oman, a high-income country in the Eastern Mediterranean Region (EMR), implemented a robust contact tracing (CT) system for COVID-19. To capitalise on Oman's experience, EMRO has developed a case study presenting the methodology used to conduct the CT activities, main functions of the system, challenges encountered, lessons learnt, and the way forward. To develop the case study, a key informant interview was conducted virtually with the CT focal point in the MoH, using a semistructured questionnaire adapted from the WHO questionnaire for the assessment of CT activities. The Oman MoH launched a CT system based on three complementary digital tools: Tarassud plus, Medical Scout and HMushrif applications. Oman's CT strategy classifies contacts into close and casual contacts. Only close contacts are listed using the Tarassud plus application, while casual contacts are requested to self-monitor for 14 days using the other two applications. With the evolution of the outbreak, Oman MoH implemented stricter policies and prioritised the follow-up of close contacts to keep the CT activity manageable. Community health workers and volunteers facilitated the CT activities through sensitisation of the local community to the follow-up process and reducing the COVID-19-associated stigma. Challenges encountered revolved around contact data management, given the offline in-operability of the applications, and lack of national risk communication guidelines to address community concerns and widespread rumours., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This review provides an overview of organic compounds detected in non-avian dinosaur fossils to date. This was enabled by the development of sensitive analytical techniques. Non-destructive methods and procedures restricted to the sample surface, e.g., light and electron microscopy, infrared (IR) and Raman spectroscopy, as well as more invasive approaches including liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), time-of-flight secondary ion mass spectrometry, and immunological methods were employed. Organic compounds detected in samples of dinosaur fossils include pigments (heme, biliverdin, protoporphyrin IX, melanin), and proteins, such as collagens and keratins. The origin and nature of the observed protein signals is, however, in some cases, controversially discussed. Molecular taphonomy approaches can support the development of suitable analytical methods to confirm reported findings and to identify further organic compounds in dinosaur and other fossils in the future. The chemical properties of the various organic compounds detected in dinosaurs, and the techniques utilized for the identification and analysis of each of the compounds will be discussed.

Background: Sustained virologic response (SVR) rates after directly acting antivirals (DAAs) for hepatitis C virus (HCV) exceed 95%. This encouraged policymakers to put plans to achieve HCV elimination by 2030. The remaining percentage of non-SVR12 can affect HCV eradication strategies in the real-world especially the compliance of large numbers of treated persons to follow up for assessment of virologic response cannot be guaranteed., Objective: We aimed to assess predictors of failure to achieve SVR after receiving sofosbuvir plus NS5A inhibitor as an important step towards achieving better HCV eradication strategies., Methods: During the period from 1st November 2018 to 1st November 2019, 1581 treatment-naive patients received sofosbuvir plus daclatasvir ± ribavirin at our unit and 10 patients were referred to us with HCV relapse after the same regimens. A total of 163 out of the 1581 patients were lost for follow-up before assessment of virologic response and excluded from the analysis. 20 out of the remaining patients failed to achieve SVR12. Data from the 30 patients with non-SVR12 were included in the case-control analysis., Results: Every unit increase in estimated creatinine clearance using modification of diet in renal disease study (MDRD) score, total bilirubin, and INR was associated with 1.03, 13.92, and 80.08 times greater odds of non-SVR12 (P<0.001, P=0.0016, P=0.02) respectively. The presence of liver cirrhosis on ultrasonography increases the odds by 10.03. (P=0.009)., Conclusion: Higher MDRD score, INR, total bilirubin, and presence of sonographic features of liver cirrhosis are predictors of failure to achieve SVR12 using sofosbuvir plus NS5A inhibitor.

Breast cancer (BC) is the most commonly diagnosed cancer worldwide and a major health concern in Egypt. There is a known association between pathogenic variants identified in breast cancer susceptibility gene ( BRCA )1 and 2 and the risk of developing BC. However, the number of studies investigating mutations in BRCA1 and BRCA2 in Egypt remains limited. Thus, the aim of the present study was to investigate the frequency of BRCA1 and BRCA2 variants in patients with BC and their relatives. For this purpose, 11 families (11 patients and 16 relatives) were included in the present study. BRCA1 and BRCA2 variants were investigated using the Ion S5 next‑generation sequencer. It was found that pathogenic variants were more frequent in patients with familial BC (FBC) than in those with sporadic BC, with 71% of variants in BRCA2 , including the first reported identification of c.9089del, c.5583&#95;5584dup, c.8243G>A and c.7976G>A pathogenic variants in Egyptian patients with BC. Pathogenic variants in relatives were confined to FBC c.1278delA, c.1960&#95;1961del, and c.1224delT, with a higher incidence of variants of uncertain significance (VUS), such as BRCA2 intron 2 c.68‑16delT. Of note, two cold spot benign variants, c.3113A>G and c.4837A>G, were repeatedly found (67%) in patients and relatives. In conclusion, to the best of our knowledge, novel pathogenic variants and VUS in Egyptian patients with BC and their high‑risk relatives were identified for the first time in the present study. These findings should be integrated with other genomic data concerning Egyptian families and carefully interpreted during genetic counseling.

Guanine nucleotide-binding proteins (G proteins) transduce extracellular signals received by G protein-coupled receptors (GPCRs) to intracellular signaling cascades. While GPCRs represent the largest class of drug targets, G protein inhibition has only recently been recognized as a novel strategy for treating complex diseases such as asthma, inflammation, and cancer. The structurally similar macrocyclic depsipeptides FR900359 (FR) and YM-254890 (YM) are potent selective inhibitors of the Gq subfamily of G proteins. FR and YM differ in two positions, FR being more lipophilic than YM. Both compounds are utilized as pharmacological tools to block Gq proteins in vitro and in vivo. However, no detailed characterization of FR and YM has been performed, which is a prerequisite for the compounds' translation into clinical application. Here, we performed a thorough study of both compounds' physicochemical, pharmacokinetic, and pharmacological properties. Chemical stability was high across a large range of pH values, with FR being somewhat more stable than YM. Oral bioavailability and brain penetration of both depsipeptides were low. FR showed lower plasma protein binding and was metabolized significantly faster than YM by human and mouse liver microsomes. FR accumulated in lung after chronic intratracheal or intraperitoneal application, while YM was more distributed to other organs. Most strikingly, the previously observed longer residence time of FR resulted in a significantly prolonged pharmacologic effect as compared to YM in a methacholine-induced bronchoconstriction mouse model. These results prove that changes within a molecule which seem marginal compared to its structural complexity can lead to crucial pharmacological differences., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Porphyrins are macrocyclic tetrapyrrole derivatives that are widely distributed in nature. They are often complexed with a metal ion located in the center of the ring system and may be modified by various substituents including additional rings, or by ring opening, which leads to a plethora of different functions. Due to their extended conjugated aromatic ring system, porphyrins absorb light in the visible range and therefore show characteristic colors. Well-known natural porphyrins include the red-colored heme present in hemoglobin, which is responsible for blood oxygen transport, and the chlorophylls in some bacteria and in plants which are utilized for photosynthesis. Porphyrins are mostly lipophilic pigments that display relatively high chemical stability. Therefore, they can even survive hundreds of millions of years. The present review article provides an overview of natural porphyrins, their chemical structures, and properties. A special focus is put on porphyrins discovered in the fossil record. Examples will be highlighted, and information on their chemical analysis will be provided. We anticipate that the development of novel analytical methods with increased sensitivity will prompt new discoveries of porphyrins in fossils., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

RNA modifications play a fundamental role in cellular function. Pseudouridylation, the most abundant RNA modification, is catalyzed by the H/ACA small ribonucleoprotein (snoRNP) complex that shares four core proteins, dyskerin (DKC1), NOP10, NHP2, and GAR1. Mutations in DKC1 , NOP10 , or NHP2 cause dyskeratosis congenita (DC), a disorder characterized by telomere attrition. Here, we report a phenotype comprising nephrotic syndrome, cataracts, sensorineural deafness, enterocolitis, and early lethality in two pedigrees: males with DKC1 p.Glu206Lys and two children with homozygous NOP10 p.Thr16Met. Females with heterozygous DKC1 p.Glu206Lys developed cataracts and sensorineural deafness, but nephrotic syndrome in only one case of skewed X-inactivation. We found telomere attrition in both pedigrees, but no mucocutaneous abnormalities suggestive of DC. Both mutations fall at the dyskerin-NOP10 binding interface in a region distinct from those implicated in DC, impair the dyskerin-NOP10 interaction, and disrupt the catalytic pseudouridylation site. Accordingly, we found reduced pseudouridine levels in the ribosomal RNA (rRNA) of the patients. Zebrafish dkc1 mutants recapitulate the human phenotype and show reduced 18S pseudouridylation, ribosomal dysregulation, and a cell-cycle defect in the absence of telomere attrition. We therefore propose that this human disorder is the consequence of defective snoRNP pseudouridylation and ribosomal dysfunction., Competing Interests: The authors declare no competing interest.

Context: Mutations in LAMB2, encoding the basement membrane protein, laminin β2, are associated with an autosomal recessive disorder characterized by congenital nephrotic syndrome, ocular abnormalities, and neurodevelopmental delay (Pierson syndrome)., Case Description: This report describes a 12-year-old boy with short stature, visual impairment, and developmental delay who presented with macroscopic hematuria and albuminuria. He had isolated growth hormone deficiency, optic nerve hypoplasia, and a small anterior pituitary with corpus callosum dysgenesis on his cranial magnetic resonance imaging, thereby supporting a diagnosis of optic nerve hypoplasia syndrome. Renal histopathology revealed focal segmental glomerulosclerosis. Using next-generation sequencing on a targeted gene panel for steroid-resistant nephrotic syndrome, compound heterozygous missense mutations were identified in LAMB2 (c.737G>A p.Arg246Gln, c.3982G>C p.Gly1328Arg). Immunohistochemical analysis revealed reduced glomerular laminin β2 expression compared to control kidney and a thin basement membrane on electron microscopy. Laminin β2 is expressed during pituitary development and Lamb2-/- mice exhibit stunted growth, abnormal neural retinae, and here we show, abnormal parenchyma of the anterior pituitary gland., Conclusion: We propose that patients with genetically undefined optic nerve hypoplasia syndrome should be screened for albuminuria and, if present, screened for mutations in LAMB2., (© Endocrine Society 2019.)

Prostate cancer (PCa) is a genetically heterogeneous cancer entity that causes challenges in pre-treatment clinical evaluation, such as the correct identification of the tumor stage. Conventional clinical tests based on digital rectal examination, Prostate-Specific Antigen (PSA) levels, and Gleason score still lack accuracy for stage prediction. We hypothesize that unraveling the molecular mechanisms underlying PCa staging via integrative analysis of multi-OMICs data could significantly improve the prediction accuracy for PCa pathological stages. We present a radiogenomic approach comprising clinical, imaging, and two genomic (gene and miRNA expression) datasets for 298 PCa patients. Comprehensive analysis of gene and miRNA expression profiles for two frequent PCa stages (T2c and T3b) unraveled the molecular characteristics for each stage and the corresponding gene regulatory interaction network that may drive tumor upstaging from T2c to T3b. Furthermore, four biomarkers ( ANPEP , mir-217 , mir-592 , mir-6715b ) were found to distinguish between the two PCa stages and were highly correlated (average r = ± 0.75) with corresponding aggressiveness-related imaging features in both tumor stages. When combined with related clinical features, these biomarkers markedly improved the prediction accuracy for the pathological stage. Our prediction model exhibits high potential to yield clinically relevant results for characterizing PCa aggressiveness., Competing Interests: The authors declare no conflict of interest.

For utilization of lactose in salted and unsalted cheese whey, intergeneric protoplast fusion between lactose nonfermenting, salt-tolerant Saccharomyces cerevisiae ATCC4126 and lactose fermenting Kluyveromyces lactis CBS683 was carried out. The fusion process gave rise to new hybrid yeast strains that revealed higher significant DNA contents than parental strains. The recombinants showed growth on either lactose or sucrose. The ethanol yields by some recombinants were 5.55% from sweet whey and 4.66% from salted whey containing up to 6% sodium chloride compared to 4.15 and 2.86% for parental K. lactis CBS683, respectively.

Temperature, mono- and disaccharides affected lipids, biomass production as well as odd-chain and unsaturated fatty acids contents of Candida tropicalis. With various sugars as carbon sources at 30 degrees C, the order for biomass production was, galactose greater than glucose greater than sucrose greater than fructose greater than lactose, while lipids production/g biomass decreased as follows: galactose, glucose, sucrose, fructose and lactose. On the other hand, the odd-chain fatty acids contents decreased in the following order: fructose, sucrose, glucose and lactose. Lowering the temperature of cultivation to 15 degrees C, decreased biomass and lipids production. However, a notable decrease in odd-chain fatty acids contents was detected.

A cell-bound lipase from the mould Aspergillus niger was isolated and purified to homogeneity as judged by disc electrophoresis on a Sephadex G-75 column. Molecular weight determination and electrophoretic mobility (Rf value) indicated that the enzyme differed from that secreted extracellularly. The cell-bound lipase showed a higher capacity than the extracellular enzyme for glyceride synthesis, and reacted in an opposite manner in the synthetic reaction compared with the extracellular enzyme.