Miracle-dz/UniFAR-FTUs huggingface dataset:
A partial loss-of-function variant in GNRNR gene in a Chinese cohort with idiopathic hypogonadotropic hypogonadism

Background Idiopathic hypogonadotropic hypogonadism (IHH) is a rare genetic disease attributed to the disorder of hypothalamic-pituitary-gonadal axis. Mutations in the GNRHR gene are one of the most common genetic causes of IHH. Herein, we aimed to investigate GNRHR variants in a Chinese cohort with IHH, and to characterize them at the molecular level. Methods A total of 153 IHH patients were recruited, and variants were detected using a tailored next-generation sequencing panel. GNRHR rare sequencing variant (RSV) was verified using Sanger sequencing. Phenotypic features and therapeutic outcomes of patients were followed up. In order to examine the pathogenicity of the GNRHR RSV, we performed conservative analysis, crystal structure prediction, expression analysis as well as the assessment of ERK1/2 activation and IP3/Ca2+ response. Results The same heterozygous RSV (p.R240Q) in GNRHR was identified in four sporadic IHH patients. These patients exhibited different severity of testicular development and hormone profile. hCG treatment was effective in improving gonadal development, serum testosterone, and semen quality. The GNRHR RSV has no effect on the expression of mRNA and protein, whereas damaged ERK1/2 activation and inositol triphosphate/calcium signaling. Conclusions The study expands GNRHR mutation spectrum in IHH patients, and reveals that the GNRHR RSV is a partial loss-of-function mutation. Although this heterozygous RSV may not have a significant influence on the pathogenesis of IHH, but its homozygous/ compound status should be paid attention in this research field.
Adaptive radiation and burst speciation of hillstream cyprinid fish Garra in African river

Adaptive radiation of fishes was long thought to be possible only in lacustrine environments. Recently, several studies have shown that also riverine and stream environments provide the ecological opportunity for adaptive radiation. In this study, we report on a riverine adaptive radiation of six ecomorphs of cyprinid hillstream fishes of the genus Garra in a river located in the Ethiopian Highlands in East Africa. Garra are predominantly highly specialized algae-scrapers with a wide distribution ranging from Southeastern Asia to Western Africa. However, adaptive phenotypic diversification in mouth type, sucking disc morphology, gut length and body shape have been found among these new species in a single Ethiopian river. Moreover, we found two novel phenotypes of Garra (‘thick-lipped’ and ‘predatory’) that were not described before in this species-rich genus (>160 species). Mitochondrial and genome-wide data suggest monophyletic, intra-basin evolution of Garra phenotypic diversity with signatures of gene flow from other local populations. Although sympatric ecomorphs are genetically distinct and can be considered to being young species as suggested by genome-wide SNP data, mtDNA was unable to identify any genetic structure suggesting a recent and rapid speciation event. Furthermore, we found evidence for a hybrid origin of the novel ‘thick-lipped’ phenotype, as being the result of the hybridization of two other sympatrically occurring species. Here we highlight how, driven by ecological opportunity, an ancestral trophically highly specialized lineage is likely to have rapidly adaptively radiated in a riverine environment, and that this radiation was promoted by the evolution of novel feeding strategies.
Mesoporous Carbon as effective and sustainable catalyst for fine chemistry

espanolEs conocido que el carbon activado por su desarrollada porosidad es un material prometedor para varias aplicaciones, desde la adsorcion a la catalisis. La investigacion en este campo se ha intensificado en los ultimos anos, en busca de nuevas y mejoradas caracteristicas y aplicaciones. Nuestro grupo de investigacion, recientemente rebautizado grupo de materiales para la adsorcion y catalisis (MAC) en LAQV-REQUIMTE, tambien ha dedicado muchos trabajos de investigacion en este tema, y ha desarrollado varios trabajos en colaboracion con otros grupos de investigacion nacional e internacional. Entre los distintos intereses de investigacion de nuestro grupo se encuentra el estudio de las propiedades cataliticas de materiales de carbono y especificamente, de carbones mesoporosos. Algunos de los resultados mas prometedores han sido seleccionados y se resumen aqui. Estos demuestran que el carbon mesoporoso es un catalizador heterogeneo eficiente y respetuoso con el medio ambiente EnglishIt is well known that activated carbon with welldeveloped porosity is a promising material that have been used for several applications, from adsorption to catalysis. Research in this field has intensified in recent years, looking for new and improved characteristics and applications. Our research group, recently renamed Materials for Adsorption and Catalysis group (MAC) in LAQV-REQUIMTE, has also devoted many research work in this subject, and has developed several collaboration works with other national and international research groups in the field. Among our research group interests there is the study of catalytic properties of carbon materials and specifically mesoporous carbon. Some of the promising results were selected and summarized here, demonstrating that mesoporous carbon is an efficient and environmentally friendly heterogeneous catalyst.
Robust IgM responses following vaccination are associated with prevention of Mycobacterium tuberculosis infection in macaques

Development of an effective tuberculosis (TB) vaccine has suffered from an incomplete understanding of the correlates of protection against Mycobacterium tuberculosis (Mtb). However, recent work has shown that compared to standard intradermal Bacille Calmette-Guerin (BCG) vaccination, intravenous (IV) BCG vaccination provides nearly complete protection against TB in rhesus macaques. While studies have focused on cellular immunity in this setting, the antibody response elicited by IV BCG vaccination remains incompletely defined. Using an agnostic antibody profiling approach, here we show that IV BCG drives superior antibody responses in the plasma and the bronchoalveolar lavage fluid (BAL). While IV BCG immunization resulted in the broad expansion of antibody titers and effector functions, surprisingly, IgM titers were among the strongest markers of reduced bacterial burden in the plasma and BAL of BCG immunized animals. Moreover, IgM immunity was also enriched among animals receiving protective vaccination with an attenuated Mtb strain. Finally, a LAM-specific IgM monoclonal antibody reduced Mtb survival in vitro. Collectively, these data highlight the potential importance of IgM responses as a marker and as a functional mediator of protection against TB.
Mini Review: Bacterial Membrane Composition and Its Modulation in Response to Stress

Antibiotics and other agents that perturb the synthesis or integrity of the bacterial cell envelope trigger compensatory stress responses. Focusing on Bacillus subtilis as a model system, this mini-review summarizes current views of membrane structure and insights into how cell envelope stress responses remodel and protect the membrane. Altering the composition and properties of the membrane and its associated proteome can protect cells against detergents, antimicrobial peptides, and pore-forming compounds while also, indirectly, contributing to resistance against compounds that affect cell wall synthesis. Many of these regulatory responses are broadly conserved, even where the details of regulation may differ, and can be important in the emergence of antibiotic resistance in clinical settings.
Independent dynamics of slow, intermediate, and fast intracranial EEG spectral activities during human memory formation

A wide spectrum of brain rhythms are engaged throughout the human cortex in cognitive functions. How the rhythms of various low and high frequencies are spatiotemporally coordinated across the human brain during memory processing is inconclusive. They can either be coordinated together across a wide range of the frequency spectrum or induced in specific bands. We used a large dataset of human intracranial electroencephalography (iEEG) to parse the spatiotemporal dynamics of spectral activities induced during formation of verbal memories. Encoding of words for subsequent free recall activated slow theta, intermediate alpha and beta, and fast gamma frequency power in discrete cortical sites. A majority of the electrode sites recorded activity in only one of these frequencies, except for the visual cortex where spectral power was induced across multiple bands. Each frequency band showed characteristic dynamics of the induced power specific to cortical area and hemisphere. The power of the low, intermediate, and fast activities propagated in distinct spatiotemporal patterns across the visual, temporal and prefrontal cortical areas as the words were presented for encoding. Our results suggest anatomically and temporally distributed spectral activities in the formation of human memory.
Autistic Personality Traits and Treatment Outcome for Alcohol Use Disorders

Abstract The importance of personality traits for the outcome of psychiatric treatment, including treatment for alcohol use disorder (AUD), has been widely acknowledged. Also, research on autism spectrum disorders has evolved in recent years, emphasizing that the behavioral traits within these neuropsychiatric disorders exist on a dimension both within and outside the boundaries of psychopathology. In the present study, the relationship between personality traits associated with autistic functioning and level of alcohol use among patients before and after concluded AUD treatment was investigated. The participants (n = 165, diagnosed with AUD) were part of a longitudinal project on AUD treatment. Data from personality questionnaires (Structured Clinical Interview of Personality Disorders II and Temperament and Character Inventory) were used to assess autistic personality traits (APTs) based on behavior within Wing’s triad, which were related to background and treatment outcome. The chosen APT items illustrated a personality functioning with an emphasis on social interaction and rigidity. Only certain included questions were indicative of still having a problematic drinking pattern 2.5 years after treatment entry, which adhered to phobic, obsessive-compulsive, and schizoid personality traits, as well as rigidity/stubbornness. Albeit with modest influence, the degree of APTs was associated with heavier drinking at treatment entry, and symptoms relating to social interaction and rigidity were associated with still having a problematic drinking pattern 2.5 years after treatment entry. A higher degree of such traits may result in having problems taking advice from others and establishing treatment alliance, important parts of treatment efficacy, making assessment of such traits relevant to clinicians.
Glioma Biopsy Based on Hybrid Dual Time-Point FET-PET/MRI—A Proof of Concept Study

Neuroimaging based on O-[2-(18F)fluoroethyl]-l-tyrosine (FET)-PET provides additional information on tumor grade and extent compared with MRI. Dynamic PET for biopsy target selection further improves results but is often clinically impractical. Static FET-PET performed at two time-points may be a good compromise, but data on this approach are limited. The aim of this study was to compare the histology of lesions obtained from two challenging glioma patients with targets selected based on hybrid dual time-point FET-PET/MRI. Five neuronavigated tumor biopsies were performed in two difficult cases of suspected glioma. Lesions with (T1-CE) and without contrast enhancement (T1 and T2-FLAIR) on MRI were selected. Dual time-point FET-PET imaging was performed 5–15 min (PET10) and 45–60 min (PET60) after radionuclide injection. The most informative FET-PET/MRI images were coregistered with MRI in time of biopsy planning. Five biopsy targets (three from high uptake and two from moderate uptake FET areas) thought to represent the most malignant sites and tumor extent were selected. Histopathological findings were compared with FET-PET and MRI images. Increased FET uptake in the area of non-CE locations on MRI correlated well with high-grade gliomas localized as far as 3 cm from T1-CE foci. Selecting a target in the motor cortex based on FET kinetics defined by dual time-point PET resulted in a grade IV diagnosis after previous negative biopsies based on MRI. An additional grade III diagnosis was obtained from an area of glioma infiltration with moderate FET uptake (between 1 and 1.25 SUV). These findings seem to show that dual time-point FET-PET-based biopsies can provide additional and clinically useful information for glioma diagnosis. Selection of targets based on dual time-point images may be useful for determining the most malignant tumor areas and may therefore be useful for resection and radiotherapy planning.
Ignition, flame structure and near-wall burning in transverse hydrogen jets in supersonic crossflow

We have investigated the properties of transverse sonic hydrogen jets in high-temperature supersonic crossflow at jet-to-crossflow momentum flux ratios $J$ between 0.3 and 5.0. The crossflow was held fixed at a Mach number of 2.4, 1400 K and 40 kPa. Schlieren and $\text{OH}^{\ast }$ chemiluminescence imaging were used to investigate the global flame structure, penetration and ignition points; $\text{OH}$ planar laser-induced fluorescence imaging over several planes was used to investigate the instantaneous reaction zone. It is found that $J$ indirectly controls many of the combustion processes. Two regimes for low ( ${<}1$ ) and high ( ${>}3$ ) $J$ are identified. At low $J$ , the flame is lifted and stabilizes in the wake close to the wall possibly by autoignition after some partial premixing occurs; most of the heat release occurs at the wall in regions where $\text{OH}$ occurs over broad regions. At high $J$ , the flame is anchored at the upstream recirculation region and remains attached to the wall within the boundary layer where $\text{OH}$ remains distributed over broad regions; a strong reacting shear layer exists where the flame is organized in thin layers. Stabilization occurs in the upstream recirculation region that forms as a consequence of the strong interaction between the bow shock, the jet and the boundary layer. In general, this interaction – which indirectly depends on $J$ because it controls the jet penetration – dominates the fluid dynamic processes and thus stabilization. As a result, the flow field may be characterized by a flame structure characteristic of multiple interacting combustion regimes, from (non-premixed) flamelets to (partially premixed) distributed reaction zones, thus requiring a description based on a multi-regime combustion formulation.
Identification of BRCA1:c.5470_5477del as a Founder Mutation in Chinese Ovarian Cancer Patients

Predisposition of germline BRCA1/2 mutations (gBRCAMUT ) increases the risk of breast and ovarian cancer in females, but the mutation prevalence and spectrum are highly ethnicity-specific with different recurrent mutations being reported in different populations. Hereby, we performed hybridization-based target sequencing of BRCA1/2 in 530 ovarian cancer patients from Henan, the central region of China, followed by haplotype analysis of six short tandem repeat (STR) markers in the patients with recurrent mutations to determine their founder effect. About 28.3% (150/530) of the OC patients in our cohort harbored gBRCAMUT ; of the 151 mutations, 117 in BRCA1 and 34 in BRCA2, identified in this study, BRCA1:c. 5470_5477del, c. 981_982del, and c. 4065_4068del are the top three mutants, recurrently detected in eight, seven, and six independent patients respectively. Haplotype analysis identified a region of 0.6 MB genomic length covering BRCA1 highly conserved across all eight carriers of BRCA1:c. 5470_5477del, but not c. 981_982del, suggesting a consequence of founder effect. Retrospective analysis in a subgroup of serous ovarian cancer patients revealed gBRCAMUT status was not associated with the progression-free survival (PFS); instead, an expression of Ki-67% ≥50% was associated with a shorter PFS (p = 0.041). In conclusion, patients with pathogenic or likely pathogenic gBRCAMUT account for 28.3% of the OC cases from Henan, and BRCA1:c. 5470_5477del, the most frequently detected mutation in Henan patients, is a founder mutation in the population.
Field assessment of the risk of feral cat baits to nontarget species in eastern Australia

Feral cats (Felis catus) pose a significant threat to wildlife, agriculture, and human health through predation, disease transmission, and competition with native animals. Controlling feral cats and their impacts, however, is challenging. New and emerging 1080‐based feral cat baits have shown promising results in western and central Australia; however, the safety of these new baits for nontarget species in eastern Australia, where many native animals are more sensitive to compound 1080 (sodium fluoroacetate) than their western conspecifics, has not been assessed. We investigated the uptake of 499 toxic Eradicat® baits by nontarget animals across five different eastern Australian environs and the uptake of nontoxic Eradicat and Hisstory® baits at an additional two sites. Using field‐based observations of species eating or removing baits, we determined that 13 nontarget species (eight mammals, four birds, and one reptile) were at high risk of individual mortality, with individuals of 11 of those 13 species (seven mammals, four birds) observed consuming enough toxic Eradicat in a single visit to ingest a lethal dose of 1080. Feral cats (the target species) consumed only 3.1% of monitored baits, which was only 52% of the 31 baits they encountered. We recommend undertaking targeted population monitoring of species identified at high risk of individual mortality, to determine whether Eradicat baits present a population‐level risk to these species. Our findings suggest that the small‐sized Eradicat baits present a greater risk to nontarget species in eastern Australia than the larger traditional 1080‐based meat baits used for the control of wild dogs and foxes. Our study highlights the importance of performing risk assessments for different bait types, even when the same toxin is used, and of performing site‐specific nontarget risk assessments of new baits such as Eradicat to assist developing guidelines for their safe and effective use in different environs. Integr Environ Assess Manag 2022;18:224–244. © 2021 State of Queensland. Integrated Environmental Assessment and Management © 2021 SETAC.
SARS-CoV-2 cell-to-cell infection is resistant to neutralizing antibodies

The COVID-19 pandemic caused by SARS-CoV-2 has posed a global threat to human lives and economics. One of the best ways to determine protection against the infection is to quantify the neutralizing activity of serum antibodies. Multiple assays have been developed to validate SARS-CoV-2 neutralization; most of them utilized lentiviral or vesicular stomatitis virus-based particles pseudotyped with the spike (S) protein, making them safe and acceptable to work with in many labs. However, these systems are only capable of measuring infection with purified particles. This study has developed a pseudoviral assay with replication-dependent reporter vectors that can accurately quantify the level of infection directly from the virus producing cell to the permissive target cell. Comparative analysis of cell-free and cell-to-cell infection revealed that the neutralizing activity of convalescent sera was more than tenfold lower in cell cocultures than in the cell-free mode of infection. As the pseudoviral system could not properly model the mechanisms of SARS-CoV-2 transmission, similar experiments were performed with replication-competent coronavirus, which detected nearly complete SARS-CoV-2 cell-to-cell infection resistance to neutralization by convalescent sera. Based on available studies, this is the first attempt to quantitatively measure SARS-CoV-2 cell-to-cell infection, for which the mechanisms are largely unknown. The findings suggest that this route of SARS-CoV-2 transmission could be of great importance for treatment and prevention of COVID-19. Importance Immune surveillance of viral or bacterial infections is largely mediated by neutralizing antibodies. Antibodies against the SARS-CoV-2 spike protein are produced after vaccination or infection, but their titers only partly reflect the degree of protection against infection. To identify protective antibodies, a neutralization test with replicating viruses or pseudoviruses (PVs) is required. This study developed lentiviral-based PV neutralization assays that, unlike similar systems reported earlier, enable quantitative measurement of SARS-CoV-2 neutralization in cell cocultures. Using both PVs and replication-competent virus, it was demonstrated that SARS-CoV-2 cell-to-cell infection is considerably more resistant to serum neutralization than infection with purified viral particles. The tests are easy to set up in many labs, and are believed to be more informative for monitoring SARS-CoV-2 collective immunity or entry inhibitor screening.
Gas Seepage-Induced Features in the Hypoxic/Anoxic, Shallow, Marine Environment of Amfilochia Bay, Amvrakikos Gulf (Western Greece)

Amfilochia Bay (Eastern Amvrakikos Gulf, Western Greece), a complex marine area affected by tectonism, was investigated for seabed seepage manifestations and for possible inter-relationships between shallow gas accumulations and hypoxia. For this purpose, an integrated research methodology that combined geophysical, geochemical, and hydrographic surveys was applied. Marine geophysical and bathymetric surveys led to the discovery of a gas-induced pockmark group in the study area. Oceanographic surveying confirmed that the bay is hypoxic/anoxic below a depth of 15 m (dissolved oxygen from ~4 to 60 μM). Very weak CH4 seepage was detected in correspondence to the pockmark group that seemed to slightly enhance the hypoxic environment locally and close to the seabed, with no effect in shallower waters and the oxycline. Methane isotopic analysis showed variable carbon isotopic composition (from −41‰ to −86‰) which could be either related to differential CH4 oxidation or mixing between microbial and thermogenic gas. However, the pathway of degassing is clearly related to the fault-controlled pockmark group. A protrusion mound, which has erroneously been reported as a submarine “volcano” since 1876, could be the result of mud volcanism based on the geophysical data of this study.