An Iron Age Scabbard Chape from Liss, Hampshire: A Northern Artefact from a Southern Find-spot

In 2018 an Iron Age scabbard chape was reported to the Portable Antiquities Scheme, having been discovered during metal-detecting on cultivated land in the parish of Liss, east Hampshire. Although the object is an isolated find, and no other components of the scabbard were discovered, it is a significant discovery. This is because it represents the most southerly evidence for a group of scabbards which are overwhelmingly distributed between the rivers Forth and Humber. This short account provides details of the object and comments on its regional and national significance.

SYRINGOMYELIA IN NEUROMYELITIS OPTICA SEROPOSITIVE FOR AQUAPORIN-4 ANTIBODY: A CASE REPORT

Neuromyelitis Optica (previously called Devics disease) is an autoimmune-induced demyelinating disorder of the central nervous system that primarily affects the optic nerves and spinal cord. This manuscript presents a case of a 28-yearold female patient who clinically presented with acute lower extremity weakness and numbness associated with unilateral impairment of vision. Later in the course of the disease, magnetic resonance imaging of the cervico-thoracic spine showed multi-level abnormal non-enhancing and enhancing lesions from levels C3 to T8 levels which were identified to be combined transverse myelitis and cord syrinx. An anti-aquaporin-4 receptor antibody was obtained and yielded to be seropositive. Given the patients clinical manifestations, combined with imaging and laboratory examinations, led to a diagnosis of Neuromyelitis Optica (NMO). The patient was managed with high-dose steroids. The significant discovery of anti-aquaporin-4 antibodies served as a key factor in the NMO immunopathogenesis. It is currently regarded as a specific biomarker of the diagnostic process, making it distinguishable from multiple sclerosis. This case highlights the mechanism of formation of a fluid-filled syrinx-like cavity in the cord in the setting of Neuromyelitis Optica.

Note on the only known record of a cupulate seed from the Middle Pennsylvanian Sydney Coalfield, Nova Scotia, Canada

The only known lyginopterid cupulate seed collected from the Middle Pennsylvanian Sydney Coalfield in Nova Scotia, Canada, comprises a coalified cupule surrounding an ovate structure 3×2 mm in size that is interpreted as an ovule. The ovule is white, reflecting its calcitic mode of preservation, and lacks cellular remains. As the specimen is incomplete, a detailed taxonomic determination is not possible, but its affinities lie within the lyginopterid (or hydrasperman) pteridosperms. This significant discovery of a lyginopterid pteridosperm aug-ments previous accounts of medullosalean pteridosperms from the flora of Sydney Coalfield.

Spatial modeling of extinct Southeast Asian Hobbit Homo floresiensis habitat suitability based on its diet availability and climatic parameters as a proxy

The discovery of a new prehistoric species of the genus Homo remains a significant matter of intense interest. One of significant discovery recently is the Homo floresiensis, representing a small-bodied and small-brained hominin, excavated, and found in Liang Bua Cave in Flores Island, East Nusa Tenggara, Indonesia. This species height was only about 106 cm (3'6") and the weight was 30-40 kg (66-86 lbs). H. floresiensis was known consumed extant murine rodents as its diets as this was evidence found in Liang Bua Cave. Then this study aims to model the H. floresiensis suitable habitat using maximum entropy method and 2 extant murine rodents, Rattus exulans and R. rattus as a proxy. The results show that the most suitable habitats for H. floresiensis indicated by suitable habitat values close to 1 were concentrated in the central of Flores Island that was overlapped with mountainous areas with elevation ranging from 1500 to 2000 m. These suitable habitats were also overlapped with dense vegetation covers, volcanic rock, and Kiro rock formation. Climatic parameters that limit the distributions of H. floresiensis were annual mean temperature, isothermality, minimum temperature of coldest period, and precipitation seasonality. Parts of Flores Island with the low temperature below 20 0C were favorable for H. floresiensis while an increase in isothermality limits the H. floresiensis distributions

NDRG1 enhances the sensitivity of cetuximab by modulating EGFR trafficking in colorectal cancer

N-myc downstream-regulated gene 1 (NDRG1) is a key regulator that interacts with many classic tumor signaling pathways, including some molecules downstream of the epidermal growth factor receptor (EGFR). However, whether NDRG1 is involved in the mechanism of resistance to cetuximab (CTX), the first monoclonal antibody targeting the EGFR has not been reported. Here, we found that NDRG1 enhanced the sensitivity of CTX in colorectal cancer (CRC) cell lines. Afterwards, we determined the underlying mechanism of this phenomenon. We demonstrated that NDRG1 inhibited the expression of EGFR; blocked EGFR phosphorylation and reduced the EGFR distribution in the cell membrane, cytoplasm and nucleus. And then, NDRG1 suppressed the EGFR downstream signaling: RAS/RAF/ERK and PI3k/AKT/mTOR pathways. Moreover, we discovered that NDRG1 attenuated the endocytosis and degradation of EGFR induced by caveolin-1 (Cav1). Additionally, our findings were further observed in an animal model and human tissues. Our results represent a potentially significant discovery that explains the mechanisms of NDRG1 in CTX resistance. NDRG1 could be a promising biomarker to predict optimum responses to CTX, and a key target to enhance CTX activity in the treatment of metastatic CRC (mCRC).

More About Gorchakov, Prokofiev’s Secretary

Цель статьи — представить новые сведения о секретаре Сергея Прокофьева Георгии Николаевиче Горчакове (1902–1995), сосредоточенные в неизвестных документальных материалах. Это был музыкант, который расшифровывал музыкальные и литературные рукописи Прокофьева, писал под его диктовку, в течение нескольких лет был проводником литературной и музыкальной мысли композитора, довел до стадии завершения несколько крупных прокофьевских партитур. Их связывало и общее вероучение, которому оба были привержены: Христианская наука. Письма Горчакова — его рассказы Прокофьеву о себе — обновляют знание о повседневном существовании обычных людей русской эмиграции. Они затрагивают не только мир музыкальный, но и непарадную сторону жизни Лазурного берега, «мореходную» тему, неизвестный прежде мотив скаутского движения: оно, оказывается, интересовало Прокофьева, у которого подрастали сыновья. Конечно, картинки общения Прокофьева и Горчакова не могли обойтись без зарисовок каждодневной прозаической жизни музыкального издательства, волнений по поводу грядущего концерта, для которого прислали не все оркестровые партии, других колоритных подробностей. Событием в прокофьевской историографии можно считать уточнение сроков выхода в свет «Вещей в себе». The aim of the article is to present a new information about Prokofiev’s secretary — Georgiy Nikolaevich Gorchakov in the analysis of previously unknown documentary materials. He was the musician, who deciphered Prokofiev’s sheet music and literary manuscripts, and who took his dictation. For years he was an agent of the composer’s musical and literary ideas and he brought to completion some large-scale Prokofiev’s scores. Besides, they were bound by the same belief — Christian Science. Gorchakov’s letters — his narrations to Prokofiev about himself — update the knowl edge about ordinary Russian people’s immigration experience. They tackle not only the world of music, but also Côte d’Azur’s everyday life: navigation and scouting, in which Prokofiev — a father of growing boys — appeared to be interested. Certainly the descrip tion of Prokofiev and Gorchakov’s communication wouldn’t be complete without outlining the mundane everyday life of the music publishing house and nerve-wracking preparations for the coming concert which was missing some orchestral parts, and other colorful details. A more accurate date for the publication of Things in Themselves could be considered a significant discovery in Prokofiev’s historiography.

Spectrum of DICER1 Germline Pathogenic Variants in Ovarian Sertoli–Leydig Cell Tumor

Sertoli–Leydig Cell Tumors (SLCTs) are rare ovarian sex cord-stromal neoplasms, which predominantly affect adolescents and young female adults. The SLCTs clinical diagnosis and treatment remains challenging due to the rarity and the varied presentation. A large majority of SLCTs are unilateral, but also bilateral neoplasms have been reported, sometimes in the context of DICER1 syndrome. In fact, the most significant discovery regarding the molecular genetics basis of SLCTs was the finding of somatic and germline pathogenic variants in the DICER1 gene. The DICER1 protein is a key component of the micro-RNA processing pathway. Germline DICER1 pathogenic variants are typically inherited in an autosomal dominant pattern and are most often loss-of-function variants dispersed along the length of the gene. Contrarily, DICER1-related tumors harbor a characteristic missense “RNase IIIb hotspot” mutation occurring in trans, or, less frequently, loss of heterozygosity (LOH) event involving the wild-type allele. While DICER1 mutations have been identified in approximately 60% of SLCTs, especially in the moderately or poorly differentiated types, there are only a few case reports of ovarian SLCT with underlying germline DICER1 mutations. In this review, we focus on the molecular genetic features of SLCT, performing an extensive survey of all germline pathogenic variants modifying the whole sequence of the DICER1 gene. We point out that DICER1 genetic testing, coupled with an accurate variants classification and timely counseling, is of crucial importance in the clinical management of ovarian SLCT-affected patients.

Myelopoiesis during Solid Cancers and Strategies for Immunotherapy

Our understanding of the relationship between the immune system and cancers has undergone significant discovery recently. Immunotherapy with T cell therapies and checkpoint blockade has meaningfully changed the oncology landscape. While remarkable clinical advances in adaptive immunity are occurring, modulation of innate immunity has proven more difficult. The myeloid compartment, including macrophages, neutrophils, and dendritic cells, has a significant impact on the persistence or elimination of tumors. Myeloid cells, specifically in the tumor microenvironment, have direct contact with tumor tissue and coordinate with tumor-reactive T cells to either stimulate or antagonize cancer immunity. However, the myeloid compartment comprises a broad array of cells in various stages of development. In addition, hematopoietic stem and progenitor cells at various stages of myelopoiesis in distant sites undergo significant modulation by tumors. Understanding how tumors exert their influence on myeloid progenitors is critical to making clinically meaningful improvements in these pathways. Therefore, this review will cover recent developments in our understanding of how solid tumors modulate myelopoiesis to promote the formation of pro-tumor immature myeloid cells. Then, it will cover some of the potential avenues for capitalizing on these mechanisms to generate antitumor immunity.

Determining the Conditions for the Resource and Economic Assets Emergence Using Threshold Analysis Algorithms

The authors consider the conditions under which the geological study of the identified structures can lead to a commercial industrially significant discovery of the Deposit. To achieve this goal, a non-standard approach was chosen - determining the minimum cost-effective parameters of object development using threshold analysis algorithms. It allows you to determine, on the one hand, the limitations of cost - effective development of objects that exist at the moment, to identify critical parameters that determine the unprofitability of the project, on the other - to create conditions in which development can become cost-effective in the future, thereby forming a vector in which decisions should be made at all stages of the project implementation. Application of the approach is demonstrated on a group of promising local objects in Paleozoic deposits located in the South of Western Siberia. The conditions for effective development of the objects under consideration are obtained, the probability of their achievement is estimated, and a list of recommendations on the order of search drilling is formulated. The complexity, convenience and applicability of this approach to the problem of searching for conditions for the formation of new resource and economic assets are proved.

4D Printing of Origami Structures for Minimally Invasive Surgeries Using Functional Scaffold

Origami structures have attracted attention in biomedical applications due to their ability to develop surgical tools that can be expanded from a minimal volume to a larger and functional device. On the other hand, four-dimensional (4D) printing is an emerging technology, which involves 3D printing of smart materials that can respond to external stimuli such as heat. This short communication introduces the proof of concept of merging origami and 4D printing technologies to develop minimally invasive delivery of functional biomedical scaffolds with high shape recovery. The shape-memory effect (SME) of the PLA filament and the origami designs were also assessed in terms of deformability and recovery rate. The results showed that herringbone tessellation origami structure combined with internal natural cancellous bone core satisfies the design requirement of foldable scaffolds. The substantial and consistent SME of the 4D printed herringbone tessellation origami, which exhibited 96% recovery compared to 61% for PLA filament, was the most significant discovery of this paper. The experiments demonstrated how the use of 4D printing in situ with origami structures could achieve reliable and repeatable results, therefore conclusively proving how 4D printing of origami structures can be applied to biomedical scaffolds.