Low androgen signaling rescues genome integrity with innate immune response by reducing fertility in humans.

Development of the gonads under complex androgen regulation is critical for germ cells specification. In this work we addressed the relationship between androgens and genomic integrity determining human fertility. We used different study groups: individuals with Differences of Sex Development (DSD), including Complete Androgen Insensitivity Syndrome (CAIS) due to mutated androgen receptor (AR), and men with idiopathic nonobstructive azoospermia. Both showed genome integrity status influenced by androgen signaling via innate immune response activation in blood and gonads. Whole proteome analysis connected low AR to interleukin-specific gene expression, while compromised genome stability and tumorigenesis were also supported by interferons. AR expression was associated with predominant DNA damage phenotype, that eliminated AR-positive Sertoli cells as the degeneration of gonads increased. Low AR contributed to resistance from the inhibition of DNA repair in primary leukocytes. Downregulation of androgen promoted apoptosis and specific innate immune response with higher susceptibility in cells carrying genomic instability.

Hericium ophelieae sp. nov., a novel species of Hericium (Basidiomycota: Russulales, Hericiaceae) from the Southern Afrotemperate forests of South Africa.

A novel species of Hericium was recently collected in the Afrotemperate forests (Knysna - Amatole region) of Southern Africa. The novel species shares many similar, dentate features common to other species in Hericium, and its basidiome first appears stark white and yellows with age. However, the substrate choice and gloeocystidia and basidiospore sizes of the specimens collected were distinct from other Hericium species. This was confirmed by sequencing the ITS and 28S genetic markers, respectively. The novel species is described as Hericium ophelieae sp. nov. and appears unique as it grows on hardwoods indigenous to Southern Africa. The species has larger basidiospores and wider gloeocystidia compared to its closest relative. H. ophelieae sp. nov. is the first endemic species of the medicinal mushroom genus Hericium to be described from Southern Africa, and the second to be described from Africa, after its closest relative, H. bembedjaense, which was isolated in Cameroon. Although this is the first Hericium to be described from the Southern African region, there are likely others to be discovered, and this study highlights the need for further research into the fungal diversity of Afrotemperate environments.

Measurement of the α-Particle Monopole Transition Form Factor Challenges Theory: A Low-Energy Puzzle for Nuclear Forces?

We perform a systematic study of the α-particle excitation from its ground state 0_{1}^{+} to the 0_{2}^{+} resonance. The so-called monopole transition form factor is investigated via an electron scattering experiment in a broad Q^{2} range (from 0.5 to 5.0 fm^{-2}). The precision of the new data dramatically supersedes that of older sets of data, each covering only a portion of the Q^{2} range. The new data allow the determination of two coefficients in a low-momentum expansion, leading to a new puzzle. By confronting experiment to state-of-the-art theoretical calculations, we observe that modern nuclear forces, including those derived within chiral effective field theory that are well tested on a variety of observables, fail to reproduce the excitation of the α particle.

Development of a Business Model Resilience Framework for Managers and Strategic Decision-makers.

Following the massive impact of the Covid-19 pandemic on the global economy and on small and medium-sized enterprises (SMEs) in particular, the concept of resilience has experienced a renaissance. As an organizational concept, business model resilience describes the extent to which an organization can maintain or quickly recover its value proposition despite unexpected current or future disruptions (Palzkill-Vorbeck 2018). Although research has been conducted in this area for decades, there is still a lack of a unified framework that brings together the findings from research and links them to organizational practice. The paper addresses this gap by developing a framework for business model resilience and demonstrating its practical relevance for organizational performance during the Covid-19 pandemic in 2020. The framework includes 11 factors that characterize the resilience of an organization's business model. For managers and decision-makers, the framework is an opportunity to assess and improve the resilience of their organizations. For researchers, the framework is an important foundation for transferring the concept of business model resilience into organizational practice.

Gonadoblastoma Y locus genes expressed in germ cells of individuals with dysgenetic gonads and a Y chromosome in their karyotypes include DDX3Y and TSPY.

STUDY QUESTION: Which Y genes mapped to the 'Gonadoblastoma Y (GBY)' locus on human Y chromosome are expressed in germ cells of individuals with some Differences of Sexual Development (DSD) and a Y chromosome in their karyotype (DSD-XY groups)? SUMMARY ANSWER: The GBY candidate genes DDX3Y and TSPY are expressed in the germ cells of DSD-XY patients from distinct etiologies: patients with mixed gonadal dysgenesis (MGD) and sex chromosome mosaics (45,X0/46,XY; 46,XX/46,XY); patients with complete androgen insensitivity (CAIS), patients with complete gonadal dysgenesis (CGD; e.g. Swyer syndrome). WHAT IS KNOWN ALREADY: A GBY locus was proposed to be present on the human Y chromosome because only DSD patients with a Y chromosome in their karyotype have a high-although variable-risk (up to 55%) for germ cell tumour development. GBY was mapped to the proximal part of the short and long Y arm. TSPY located in the proximal part of the short Y arm (Yp11.1) was found to be a strong GBY candidate gene. It is expressed in the germ cells of DSD-XY patients with distinct etiologies but also in foetal and pre-meiotic male spermatogonia. However, the GBY region extends to proximal Yq11 and therefore includes probably more than one candidate gene. STUDY DESIGN, SIZE, DURATION: Protein expression of the putative GBY candidate gene in proximal Yq11, DDX3Y, is compared with that of TSPY in serial gonadal tissue sections of 40 DSD-XY individuals from the three DSD patient groups (MGD, Complete Androgen Insensitivity Syndrome [CAIS], CGD) with and without displaying malignancy. Expression of OCT3/4 in the same tissue samples marks the rate of pluripotent germ cells. PARTICIPANTS/MATERIALS, SETTING, METHOD: A total of 145 DSD individuals were analysed for the Y chromosome to select the DSD-XY subgroup. PCR multiplex assays with Y gene specific marker set score for putative microdeletions in GBY Locus. Immunohistochemical experiments with specific antisera mark expression of the GBY candidate proteins, DDX3Y, TSPY, in serial sections of the gonadal tissue samples; OCT3/4 expression analyses in parallel reveal the pluripotent germ cell fraction. MAIN RESULTS AND THE ROLE OF CHANCE: Similar DDX3Y and TSPY protein expression patterns were found in the germ cells of DSD-XY patients from each subgroup, independent of age. In CAIS patients OCT3/4 expression was often found only in a fraction of these germ cells. This suggest that GBY candidate proteins are also expressed in the non-malignant germ cells of DSD-XY individuals like in male spermatogonia. LIMITATIONS, REASONS FOR CAUTION: Variation of the expression profiles of GBY candidate genes in the germ cells of some DSD-XY individuals suggests distinct transcriptional and translational control mechanisms which are functioning during expression of these Y genes in the DSD-XY germ cells. Their proposed GBY tumour susceptibility function to transform these germ cells to pre-malignant GB/Germ Cell Neoplasia in Situ (GB/GCNIS) cells seems therefore to be limited and depending on their state of pluripotency. WIDER IMPLICATIONS OF THE FINDINGS: These experimental findings are of general importance for each individual identified in the clinic with DSD and a Y chromosome in the karyotype. To judge their risk of germ cell tumour development, OCT3/4 expression analyses on their gonadal tissue section is mandatory to reveal the fraction of germ cells still being pluripotent. Comparative expression analysis of the GBY candidate genes can be helpful to reveal the fraction of germ cells with genetically still activated Y chromosomes contributing to further development of malignancy if at high expression level. STUDY FUNDING/COMPETING INTEREST(S): This research project was supported by a grant (01GM0627) from the BMBF (Bundesministerium für Bildung und Forschung), Germany to P.H.V. and B.B. The authors have no competing interests.

In vivo implantation of a tissue engineered stem cell seeded hemi-laryngeal replacement maintains airway, phonation, and swallowing in pigs.

Laryngeal functional impairment relating to swallowing, vocalisation, and respiration can be life changing and devastating for patients. A tissue engineering approach to regenerating vocal folds would represent a significant advantage over current clinical practice. Porcine hemi-larynx were de-cellularised under negative pressure. The resultant acellular scaffold was seeded with human bone marrow derived mesenchymal stem cells and primary human epithelial cells. Seeded scaffolds were implanted orthotopically into a defect created in the thyroid cartilage in 8 pigs and monitored in vivo for 2 months. In vivo assessments consisted of mucosal brushing and bronchoscopy at 1, 2, 4, and 8 weeks post implantation followed by histological evaluation post termination. The implanted graft had no adverse effect on respiratory function in 6 of the 8 pigs; none of the pigs had problems with swallowing or vocalisation. Six out of the 8 animals survived to the planned termination date; 2 animals were terminated due to mild stenosis and deep tissue abscess formation, respectively. Human epithelial cells from mucosal brushings could only be identified at Weeks 1 and 4. The explanted tissue showed complete epithelialisation of the mucosal surface and the development of rudimentary vocal folds. However, there was no evidence of cartilage remodelling at the relatively early censor point. Single stage partial laryngeal replacement is a safe surgical procedure. Replacement with a tissue engineered laryngeal graft as a single procedure is surgically feasible and results in appropriate mucosal coverage and rudimentary vocal fold development.