Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by ...single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.
Gonadal development is a complex process that involves sex determination followed by divergent maturation into either testes or ovaries
. Historically, limited tissue accessibility, a lack of ...reliable in vitro models and critical differences between humans and mice have hampered our knowledge of human gonadogenesis, despite its importance in gonadal conditions and infertility. Here, we generated a comprehensive map of first- and second-trimester human gonads using a combination of single-cell and spatial transcriptomics, chromatin accessibility assays and fluorescent microscopy. We extracted human-specific regulatory programmes that control the development of germline and somatic cell lineages by profiling equivalent developmental stages in mice. In both species, we define the somatic cell states present at the time of sex specification, including the bipotent early supporting population that, in males, upregulates the testis-determining factor SRY and sPAX8s, a gonadal lineage located at the gonadal-mesonephric interface. In females, we resolve the cellular and molecular events that give rise to the first and second waves of granulosa cells that compartmentalize the developing ovary to modulate germ cell differentiation. In males, we identify human SIGLEC15
and TREM2
fetal testicular macrophages, which signal to somatic cells outside and inside the developing testis cords, respectively. This study provides a comprehensive spatiotemporal map of human and mouse gonadal differentiation, which can guide in vitro gonadogenesis.
A reflectarray antenna monolithically integrated with 90 RF MEMS switches has been designed and fabricated to achieve switching of the main beam. Aperture coupled microstrip patch antenna (ACMPA) ...elements are used to form a 10 × 10 element reconfigurable reflectarray antenna operating at 26.5 GHz. The change in the progressive phase shift between the elements is obtained by adjusting the length of the open ended transmission lines in the elements with the RF MEMS switches. The reconfigurable reflectarray is monolithically fabricated with the RF MEMS switches in an area of 42.46 cm 2 using an in-house surface micromachining and wafer bonding process. The measurement results show that the main beam can be switched between broadside and 40° in the H-plane at 26.5 GHz.
Extreme ultraviolet (EUV) lithography is currently entering high-volume manufacturing to enable the continued miniaturization of semiconductor devices. The required EUV light, at 13.5 nm wavelength, ...is produced in a hot and dense laser-driven tin plasma. The atomic origins of this light are demonstrably poorly understood. Here we calculate detailed tin opacity spectra using the Los Alamos atomic physics suite ATOMIC and validate these calculations with experimental comparisons. Our key finding is that EUV light largely originates from transitions between multiply-excited states, and not from the singly-excited states decaying to the ground state as is the current paradigm. Moreover, we find that transitions between these multiply-excited states also contribute in the same narrow window around 13.5 nm as those originating from singly-excited states, and this striking property holds over a wide range of charge states. We thus reveal the doubly magic behavior of tin and the origins of the EUV light.
Upon glucose restriction, eukaryotic cells upregulate oxidative metabolism to maintain homeostasis. Using genetic screens, we find that the mitochondrial serine hydroxymethyltransferase (SHMT2) is ...required for robust mitochondrial oxygen consumption and low glucose proliferation. SHMT2 catalyzes the first step in mitochondrial one-carbon metabolism, which, particularly in proliferating cells, produces tetrahydrofolate (THF)-conjugated one-carbon units used in cytoplasmic reactions despite the presence of a parallel cytoplasmic pathway. Impairing cytoplasmic one-carbon metabolism or blocking efflux of one-carbon units from mitochondria does not phenocopy SHMT2 loss, indicating that a mitochondrial THF cofactor is responsible for the observed phenotype. The enzyme MTFMT utilizes one such cofactor, 10-formyl THF, producing formylmethionyl-tRNAs, specialized initiator tRNAs necessary for proper translation of mitochondrially encoded proteins. Accordingly, SHMT2 null cells specifically fail to maintain formylmethionyl-tRNA pools and mitochondrially encoded proteins, phenotypes similar to those observed in MTFMT-deficient patients. These findings provide a rationale for maintaining a compartmentalized one-carbon pathway in mitochondria.
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•Cells lacking SHMT2 are sensitive to glucose restriction•The mitochondrial one-carbon pool supports respiration•SHMT2 loss disrupts proper translation of mitochondrially encoded proteins•Serine contributes to methionine formylation on mitochondrial initiator tRNAs
Using CRISPR/Cas9-based screening, Minton et al. identify serine catabolic enzyme SHMT2 as differentially required in low glucose. Via SHMT2, serine contributes to mitochondrial one-carbon pools, THF-based cofactors required for carbon transfer reactions including mitochondrial initiator tRNA formylation. Therefore, SHMT2 loss impacts mitochondrial translation, depleting mitochondrially encoded proteins and decreasing respiration.
The aim of this study was to determine the prevalence of diabetic peripheral neuropathy (DPN) and neuropathic pain in diabetic patients attending university outpatient clinics in Turkey. In this ...multicenter cross-sectional study, neurologic examinations and nerve conduction studies along with clinical diabetic neuropathy score, and Leeds Assessment of Neuropathic Symptoms and Signs pain scale were performed on 1,113 patients (46.2% male) from 14 centers. Prevalence of DPN determined only by clinical examination was 40.4% and increased to 62.2%, by combining nerve conduction studies with clinical examination. According to Leeds Assessment of Neuropathic Symptoms and Signs scores, neuropathic pain prevalence was 16.0% in those who reported pain. Poor glycemic control, retinopathy, microalbuminuria, hyperlipidemia, diabetic foot, and foot amputation were more commonly observed in patients with DPN. Clinical DPN affected 40.4% of diabetic patients, and neuropathic pain prevalence in diabetic patient population was 14.0%. Clinical examinations and nerve conduction studies are important components for early detection and accurate diagnosis of DPN and painful DPN.
The objective of the study was to compare the carcass characteristics, meat quality, and blood parameters of slow and fast grown female broiler chickens fed in organic or conventional production ...system. The two genotypes tested were medium slow-growing chickens (SG, Hubbard Red JA) and commercial fast-growing chickens (FG, Ross 308). Both genotypes (each represented by 400 chickens) were divided into two sub-groups fed either organic (O) or conventional (C) systems. Chickens of each genotype and system were raised in a semi environmentally controlled poultry house until 21 d of age and were assigned to 5 pens of 40 chickens each. Then, O system chickens were transferred into an open-side poultry house with an outdoor run. At 81 d of age, 10 female chickens from each genotype and from each production system (n = 40) were randomly chosen to provide material for analysis, and were weighed and brought to the slaughterhouse to assess carcass characteristics and meat quality. The blood parameters were determined by using 5 female chickens from each genotype and from each production system (n = 20). FG had the higher live weight, along with carcass, breast, and thigh-drumstick weights compared to SG (p<0.05). FG had the higher breast yield, whereas SG had the higher thigh-drumstick yield (p<0.05). The O system resulted in a higher amount of abdominal fat (p<0.05). In addition, the O system values were higher for dry matter, crude ash, crude protein, and pH(15) values in breast meat, and for crude ash, crude protein, and pH(15) values in drumstick meat (p<0.05). In addition, total saturated fatty acids, total mono-unsaturated fatty acids, and total omega 3 were significantly higher in the O system than in the C system. Thus, the O system showed a positive advantage compared to the C system regarding female chicken meat quality, primarily within the ash, protein, and total omega 3 fatty acid profiles. In conclusion, the present study indicated that the main factor affecting the carcass characteristics of female chickens was genotype, whereas the organic system contributed to enhanced meat quality. These findings provide a better understanding of the relative roles of genotype and production systems in female broiler characteristics, and might aid producers in designing their facilities to optimize yield and quality while maintaining acceptable animal welfare standards.
An experimental study of laser-produced plasmas is performed by irradiating a planar tin target by laser pulses, of 4.8 ns duration, produced from a KTP-based 2-µm-wavelength master oscillator power ...amplifier. Comparative spectroscopic investigations are performed for plasmas driven by 1-µm- and 2-µm-wavelength pulsed lasers, over a wide range of laser intensities spanning 0.5 - 5 × 10
W/cm
. Similar extreme ultraviolet (EUV) spectra in the 5.5-25.5 nm wavelength range and underlying plasma ionicities are obtained when the intensity ratio is kept fixed at I
/I
= 2.4(7). Crucially, the conversion efficiency (CE) of 2-µm-laser energy into radiation within a 2% bandwidth centered at 13.5 nm relevant for industrial applications is found to be a factor of two larger, at a 60 degree observation angle, than in the case of the denser 1-µm-laser-driven plasma. Our findings regarding the scaling of the optimum laser intensity for efficient EUV generation and CE with drive laser wavelength are extended to other laser wavelengths using available literature data.
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