bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serious mental illness in women
Authors: Almeida Marcela , Fletcher Sun J. 
Published: February 2022

Purpose of review
Psychiatric illnesses are very prevalent in the United States and impact women and men differently. In this review, we will explore some gender differences in the expression of psychopathology, discuss the most common serious mental illnesses (SMI) affecting women, and review treatment options according to specific life stages. We hope to raise awareness of these issues and consequently improve outcomes for women with serious mental illness.

Recent findings
SMI have different rates and are manifested differently in women and men because of biological, psychological, social, and cultural factors. Some SMI are more prevalent in women whereas others uniquely affect them during particular life stages. Even in disorders that have a similar prevalence in men and women or are more prevalent in men, the presentation, course, management, and repercussions can vary significantly between the two genders. Medical and psychiatric comorbidities, which directly influence treatment, prognosis, and disability, are more common in women.

Summary
Several differences in the gender expression of SMI have not yet been fully described. It is important to become familiar with important characteristics of SMI in women, including biological determinants, treatment differences, and psychosocial aspects. Recognizing gender biases, cultural considerations, and adaptive responses can help identify women at risk, promote early recognition of symptoms, and prompt interventions that may lead to improved outcomes.
At the molecular resolution with MINFLUX?
Authors: Prakash Kirti 
Published: February 2022

MINFLUX is purported as the next revolutionary fluorescence microscopy technique claiming a spatial resolution in the range of 1–3 nm in fixed and living cells. Though the claim of molecular resolution is attractive, I am concerned whether true 1 nm resolution has been attained. Here, I compare the performance with other super-resolution methods focusing particularly on spatial resolution claims, subjective filtering of localizations, detection versus labelling efficiency and the possible limitations when imaging biological samples containing densely labelled structures. I hope the analysis and evaluation parameters presented here are not only useful for future research directions for single-molecule techniques but also microscope users, developers and core facility managers when deciding on an investment for the next ‘state-of-the-art’ instrument.
This article is part of the Theo Murphy meeting issue ‘Super-resolution structured illumination microscopy (part 2)’.
Enabling single-molecule localization microscopy in turbid food emulsions
Authors: Jabermoradi Abbas , Yang Suyeon , Gobes Martijn I. , van Duynhoven John P. M. , Hohlbein Johannes 
Published: February 2022

Turbidity poses a major challenge for the microscopic characterization of food systems. Local mismatches in refractive indices, for example, lead to significant image deterioration along sample depth. To mitigate the issue of turbidity and to increase the accessible optical resolution in food microscopy, we added adaptive optics (AO) and flat-field illumination to our previously published open microscopy framework, the miCube. In the detection path, we implemented AO via a deformable mirror to compensate aberrations and to modulate the emission wavefront enabling the engineering of point spread functions (PSFs) for single-molecule localization microscopy (SMLM) in three dimensions. As a model system for a non-transparent food colloid such as mayonnaise, we designed an oil-in-water emulsion containing the ferric ion binding protein phosvitin commonly present in egg yolk. We targeted phosvitin with fluorescently labelled primary antibodies and used PSF engineering to obtain two- and three-dimensional images of phosvitin covered oil droplets with sub 100 nm resolution. Our data indicated that phosvitin is homogeneously distributed at the interface. With the possibility to obtain super-resolved images in depth, our work paves the way for localizing biomacromolecules at heterogeneous colloidal interfaces in food emulsions.This article is part of the Theo Murphy meeting issue ‘Super-resolution structured illumination microscopy (part 2)’.
The biology of imaging
Authors: Reynaud Emmanuel G. 
Published: February 2022

On the cave wall, a discrete but stunning silhouette runs across the uneven surface. Standing still for more than 45 000 years, this is a witness to the ever-enduring need of mankind to image the world around us. The biological world that feeds us is a primary source of inspiration but also an essential element to creating the imaging systems we use every day. But once obscured by the technological jargon and the thunderstorm of numbers and algorithms, those origins fade away into the background. This small piece is about a few marvellous little stories about the biology of imaging, not the debate about the origin of vision and the eye but rather about plants and animals that open the world to new dimensions of biological imaging to fully image the biological world. An eye for an eye.
This article is part of the Theo Murphy meeting issue ‘Super-resolution structured illumination microscopy (part 2)’.
Super-resolution microscopy: a brief history and new avenues
Authors: Prakash Kirti , Diederich Benedict , Heintzmann Rainer , Schermelleh Lothar 
Published: February 2022

Super-resolution microscopy (SRM) is a fast-developing field that encompasses fluorescence imaging techniques with the capability to resolve objects below the classical diffraction limit of optical resolution. Acknowledged with the Nobel prize in 2014, numerous SRM methods have meanwhile evolved and are being widely applied in biomedical research, all with specific strengths and shortcomings. While some techniques are capable of nanometre-scale molecular resolution, others are geared towards volumetric three-dimensional multi-colour or fast live-cell imaging. In this editorial review, we pick on the latest trends in the field. We start with a brief historical overview of both conceptual and commercial developments. Next, we highlight important parameters for imaging successfully with a particular super-resolution modality. Finally, we discuss the importance of reproducibility and quality control and the significance of open-source tools in microscopy.This article is part of the Theo Murphy meeting issue 'Super-resolution structured illumination microscopy (part 2)'.
Structured illumination ophthalmoscope: super-resolution microscopy on the living human eye
Authors: Schock Florian , Best Gerrit , Celik Nil , Heintzmann Rainer , Dithmar Stefan , Cremer Christoph 
Published: February 2022

In this paper, we present the prototype of an ophthalmoscope that uses structured illumination microscopy (SIM) to enable super-resolved imaging of the human retina, and give first insights into clinical application possibilities. The SIM technique was applied to build a prototype that uses the lens of the human eye as an objective to ‘super-resolve’ the retina of a living human. In our multidisciplinary collaboration, we have adapted this well-established technique in ophthalmology and successfully imaged a human retina using significantly lower light intensity than a state-of-the-art ophthalmoscope. Here, we focus on the technical implementation and highlight future perspectives of this method. A more application-oriented note for physicians on the diagnostic and disease-preventive value of this method, as well as the medical results of the clinical study carried out, will be published in a report addressed to an appropriate specialist audience.
This article is part of the Theo Murphy meeting issue ‘Super-resolution structured illumination microscopy (part 2)’.
Spatially modulated illumination microscopy: application perspectives in nuclear nanostructure analysis
Authors: Cremer Christoph , Birk Udo 
Published: February 2022

Thousands of genes and the complex biochemical networks for their transcription are packed in the micrometer sized cell nucleus. To control biochemical processes, spatial organization plays a key role. Hence the structure of the cell nucleus of higher organisms has emerged as a main topic of advanced light microscopy. So far, a variety of methods have been applied for this, including confocal laser scanning fluorescence microscopy, 4Pi-, STED- and localization microscopy approaches, as well as (laterally) structured illumination microscopy (SIM). Here, we summarize the state of the art and discuss application perspectives for nuclear nanostructure analysis of spatially modulated illumination (SMI). SMI is a widefield-based approach to using axially structured illumination patterns to determine the axial extension (size) of small, optically isolated fluorescent objects between less than or equal to 200 nm and greater than or equal to 40 nm diameter with a precision down to the few nm range; in addition, it allows the axial positioning of such structures down to the 1 nm scale. Combined with SIM, a three-dimensional localization precision of less than or equal to 1 nm is expected to become feasible using fluorescence yields typical for single molecule localization microscopy applications. Together with its nanosizing capability, this may eventually be used to analyse macromolecular complexes and other nanostructures with a topological resolution, further narrowing the gap to Cryoelectron microscopy.
This article is part of the Theo Murphy meeting issue ‘Super-resolution structured illumination microscopy (part 2)’.
An Optrode Array for Spatiotemporally Precise Large-Scale Optogenetic Stimulation of Deep Cortical Layers in Non-human Primates
Authors: Clark Andrew M. , Ingold Alexander , Reiche Christopher F. , Cundy Donald , Balsor Justin L. , Federer Frederick , McAlinden Niall , Cheng Yunzhou , Rolston John D. , Rieth Loren , Dawson Martin D. , Mathieson Keith , Blair Steve , Angelucci Alessandra 
Published: February 2022

ABSTRACTOptogenetics has transformed studies of neural circuit function, but remains challenging to apply in large brains, such as those of non-human primates (NHPs). A major challenge is delivering intense, spatiotemporally precise, patterned photostimulation across large volumes in deep tissue. Such stimulation is critical, for example, to modulate selectively deep-layer corticocortical feedback projections. To address this unmet need, we have developed the Utah Optrode Array (UOA), a 10×10 glass needle waveguide array fabricated atop a novel opaque optical interposer then bonded to an electrically addressable μLED array.In vivoexperiments with the UOA demonstrated large-scale, spatiotemporally precise, activation of deep circuits in monkey cortex. Specifically, the UOA permitted both focal (confined to single layers/columns), and widespread (multiple layers/columns) optogenetic activation of deep layer neurons, simply by varying the number of activated μLEDs and/or the irradiance. Thus, the UOA represents a powerful optoelectronic device for targeted manipulation of deep-layer circuits in NHP models.
Biogeography and Validation of species limits in Caribbean Red Bats (Vespertilionidae:Lasiurus)
Authors: Soto-Centeno J. Angel , Calderón-Acevedo Camilo A. 
Published: February 2022

AbstractDefining species limits using an integrative framework is crucial for biodiversity assessments and to maintain taxonomic stability. These approaches are robust and can be useful to also validate the status of species that are uncommon and underrepresented in biological collections. We examined the species limits and validated the taxonomic status of the Minor Red Bat (Lasiurus minor), an uncommon species originally described from four specimens. Our approach consisted of three independent lines of evidence combining genetic and phenotypic data. Phylogenetic analyses confirmed the uniqueness ofL. minorcompared to three other geographically and closely related Red Bat species. Furthermore, coalescent species delimitation supported the four Red Bat species hypothesis. Linear phenotypic analyses demonstrated thatL. minoris distinct from other Red Bats despite a morphological continuum. Finally, we reassessed the diagnosability of characters used to describeL. minorusing an objective shape analysis approach, which emphasized the support for this taxon. Based on our findings, while identification in the field could still pose a challenge, there is strong support to recognizeL. minor. This study settles a longstanding taxonomic question and provides evidence to better understand Caribbean biodiversity.
Gain-of-function, focal segmental glomerulosclerosis Trpc6 mutation minimally affects susceptibility to renal injury in several mouse models
Authors: Brown Brittney J. , Boekell Kimber L. , Stotter Brian R. , Talbot Brianna E. , Schlondorff Johannes S. 
Published: February 2022

AbstractMutations in TRPC6 are a cause of autosomal dominant focal segmental glomerulosclerosis in humans. Many of these mutations are known to have a gain-of-function effect on the non-specific cation channel function of TRPC6. In vitro studies have suggested these mutations affect several signaling pathways, but in vivo studies have largely compared wild-type and Trpc6-deficient rodents. We developed mice carrying a gain-of-function Trpc6 mutation encoding an E896K amino acid change, corresponding to a known FSGS mutation in TRPC6. Homozygous mutant Trpc6 animals have no appreciable renal pathology, and do not develop albuminuria until very advanced age. The Trpc6E896K mutation does not impart susceptibility to PAN nephrosis. The animals show a slight delay in recovery from the albumin overload model. In response to chronic angiotensin II infusion, Trpc6E896K/E896K mice have slightly greater albuminuria initially compared to wild-type animals, an effect that is lost at later time points, and a statistically non-significant trend toward more glomerular injury. This phenotype is nearly opposite to that of Trpc6-deficient animals previously described. The Trpc6 mutation does not appreciably impact renal interstitial fibrosis in response to either angiotensin II infusion, or folate-induced kidney injury. TRPC6 protein and TRPC6-agonist induced calcium influx could not be detected in glomeruli. In sum, these findings suggest that a gain-of-function Trpc6 mutation confers only a mild susceptibility to glomerular injury in the mouse.
Two-pore channel blockade by phosphoinositide kinase inhibitors YM201636 and PI-103 determined by a histidine residue near pore-entrance
Authors: Du Canwei , Guan Xin , Yan Jiusheng 
Published: February 2022

AbstractHuman two-pore channels (TPCs) are endolysosomal cation channels and play an important role in NAADP-evoked Ca2+ release and endomembrane dynamics. TPCs are activated by PI(3,5)P2, which is synthesized by PIKfyve. Here, we found that YM201636, a widely used PIKfyve inhibitor, potently inhibits PI(3,5)P2-induced human TPC2 channel Na+ currents in a dose-dependent manner with an IC50 of 0.16 μM. YM201636 also effectively inhibits the currents of a constitutively open TPC2 mutant channel, whereas it exerts no effect when applied in the channel’s closed state. A YM201636 analog, PI-103, an inhibitor of PI3K and mTOR, also inhibits human TPC2 with an IC50 of 0.64 μM. Substitution of the pore-constriction residues Leu690, Leu694 and Tyr312 by Ala reduced the effectiveness of YM201636 and PI-103 in channel inhibition. Interestingly, a His699 residue located near the cytosolic pore entrance is a key determinant for the TPC2 channels’ sensitivity to YM201636 and PI-103, whose substitution with a Phe in the human TPC1 largely accounts for the channel’s loss of inhibition by YM201636. Molecular dynamic simulation and docking analysis of YM201636’s binding to TPC2 indicated that His699 can interact with the inhibitor and facilitate the channel-blockade at the cytosolic end of the pore. We conclude that YM201636 and PI-103 directly block the TPC2’s open-state channel pore at the cytosolic entrance where the His699 is a key determinant for the blockers’ access to the pore. These findings identify two new potent TPC2 channel blockers, reveal a channel pore entrance blockade mechanism, and provide a new protein target in interpreting the pharmacological effects of these two widely used phosphoinositide kinase inhibitors.
Cerebral organoids for modeling of HSV-1-induced-multiscale neuropathology associated with Alzheimer’s disease and phenotypic rescue
Authors: Qiao Haowen , Zhao Wen , Guo Moujian , Zhu Lili , Chen Tao , Wang Jibo , Zhang Zhentao , Wu Ying , Chen Pu 
Published: February 2022

ABSTRACTHerpes simplex virus type I (HSV-1) infection is a potential risk factor involved in the pathogenesis of Alzheimer’s disease (AD) and contributes to the AD viral hypothesis. However, further understanding of the neuropathological effects of the HSV-1 infection is hampered by the limitations of existing infection models due to the distinct differences between human brains and other mammalians’ brains. Here we generated cerebral organoid models derived from pluripotent stem cells to investigate the HSV-induced pathogenesis associated with AD and the role of antiviral drugs in the phenotypic rescue. Our results identified that the HSV-1-infected cerebral organoids recapitulated multiscale neuropathology pertaining to the onset and progression of AD across the genetic, cellular, and tissue levels, including the multicellular Aβ deposition, dysregulated endogenous AD mediators, reactive gliosis, neuroinflammation, and neural loss. Furthermore, we identified that two antiviral drugs, namely Ribavirin (RBV) and Valacyclovir (VCV), inhibited HSV-1 replication and rescued the neuropathological phenotypes associated with AD in the HSV-1-infected cerebral organoids, implying their therapeutic potential to slow down the progression of AD. Our study provides a high-fidelity human-relevant in-vitro HSV-1 infection model to reconstitute the multiscale neuropathological features associated with AD and discover therapeutic drug candidates relevant to the AD viral hypothesis.IMPORTANCEAD is a progressive neurodegenerative disorder characterized by neuronal death, brain atrophy, and cognitive impairment. HSV-1 is a neurotropic double-stranded DNA virus resulting in long-term neurological sequelae in adults.There is accumulating evidence indicating that AD may be associated with HSV-1 infections. In this study, we generated human-physiologically related cerebral organoids derived from human embryonic stem cells (hESCs) to investigate the influence of HSV-1 infection on the neuropathology associated with AD. We found that the HSV-1-infected cerebral organoids could model typical neuropathological features associated with AD. Additionally, we discovered that both RBV and VCV significantly rescued the HSV-1-induced pathological phenotypes associated with AD. These findings may open new avenues of consideration related to HSV-1 infection and AD. Furthermore, the contribution of these antiviral drugs to AD linked to HSV-1 infection will provide new clues to potential new therapies.
Risk of severe COVID-19 in patients with inflammatory rheumatic diseases treated with immunosuppressive therapy in Scotland
Authors: McKeigue Paul M , Porter Duncan , Hollick Rosemary J , Ralston Stuart H , McAllister David A , Colhoun Helen M 
Published: February 2022

AbstractObjectivesTo investigate the association of severe COVID-19 in those with inflammatory rheumatic diseases (IRD) treated with immunosuppressive drugs.MethodsA list of 4633 patients on biologics and targeted synthetic (ts) DMARDs in March 2020 was linked to a case-control study that includes all cases of COVID-19 in Scotland.ResultsBy 22 November 2021 433 of the 4633 patients treated with biologics and tsDMARDs had been diagnosed with COVID-19, of whom 58 had been hospitalised. With all those in the population not on DMARDs as reference category, the rate ratio for hospitalised COVID-19 associated with DMARD treatment was 2.14 (95% CI 2.02 to 2.26) in those on conventional synthetic (cs) DMARDs, 2.01 (95% CI 1.38 to 2.91) in those on TNF inhibitors as the only biologic agent, and 3.83 (95% CI 2.65 to 5.56) in those on other biologic agents. Among those on csDMARDs, rate ratios for hospitalised COVID-19 were lowest at 1.66 (95% CI 1.51 to 1.82) in those on methotrexate and highest at 5.4 (95% CI 4.4 to 6.7) in those on glucocorticoids at average dose >10 mg/day prednisolone equivalent.ConclusionThe risk of hospitalised COVID-19 is elevated in IRD patients treated with immunosuppressive drugs. Of these drugs, methotrexate, hydroxychloroquine, and TNF inhibitors carry the lowest risk, JAK inhibitors and B-cell depleting agents a higher risk and prednisolone the highest risk. A larger study is needed to estimate reliably the risks associated with each class of biologic agent.Key messagesRisk of hospitalised COVID-19 is about twofold higher in IRD patients treated with immunosuppressive therapies – csDMARDS or biologics – than in the general population.Risk is lowest in those treated with methotrexate, hydroxychoroquine and TNF inhibitors. Of the other biologic drugs, treatment with B cell depleters and JAK inhibitors is associated with higher risk but the numbers are too small for risk associated with each drug class to be estimated reliably.The risk of severe COVID-19 with glucocorticoids at a dose greater than 10 mg/day prednisolone equivalent is higher than that of any other drug class studied.
High-Resolution Tandem Mass Spectrometry Indicates Rubisco Activase is Associated with PS I-LHC I-LHC II Membranes
Authors: Kale Ravindra S. , Sallans Larry , Frankel Laurie K. , Bricker Terry M. 
Published: February 2022

AbstractDuring proteomic investigations examining the mobile LHC II chlorophyll antenna complex associated with Photosystem I (PS I), we identified, with very high confidence, the association of Rubisco Activase with PS I-LHC I-LHC II membranes. Using very rigorous criteria (p-values ≤ 10-5), a total of fifty-three high-quality Rubisco Activase peptides were identified by high resolution tandem mass spectrometry in two biological replicates, each digested with either trypsin or chymotrypsin, independently. Using these criteria, and searching the entire spinach proteome, only proteins previously known to be associated with PS I (the PS I subunits PsaD and PsaL, Lhca1-4, Lhcb1-3), the monomeric Lhcb proteins, Lhcb4-6 (which will be discussed elsewhere), and Rubisco Activase were identified. The presence of Rubisco Activase closely associated with PS I has important implications with respect to the activation of this enzyme and, consequently, the Calvin cycle by PS I, which will be discussed.
Multi-modal single-cell and whole-genome sequencing of minute, frozen specimens to propel clinical applications
Authors: Wang Yiping , Fan Joy Linyue , Melms Johannes C. , Amin Amit Dipak , Georgis Yohanna , Ho Patricia , Tagore Somnath , Abril-Rodríguez Gabriel , Biermann Jana , Hofree Matan , Caprio Lindsay , Berhe Simon , Khan Shaheer A. , Henick Brian S. , Ribas Antoni , Taylor Alison M. , Schwartz Gary K. , Carvajal Richard D. , Azizi Elham , Izar Benjamin 
Published: February 2022

ABSTRACTSingle-cell genomics are enabling technologies, but their broad clinical application remains challenging. We report an easily adaptable approach for single-cell transcriptome and T cell receptor (TCR)-sequencing, and matched whole-genome sequencing from tiny, frozen clinical specimens. We achieve similar quality and biological outputs while reducing artifactual signals compared to data from matched fresh tissue samples. Profiling sequentially collected melanoma samples from the KEYNOTE-001 trial, we resolve cellular, genomic, and clonotype dynamics that encapsulate molecular patterns of tumor evolution during anti-PD-1 therapy. To demonstrate applicability to banked biospecimens of rare diseases, we generate a large uveal melanoma liver metastasis single-cell and matched WGS atlas, which revealed niche-specific impairment of clonal T cell expansion. This study provides a foundational framework for propelling single-cell genomics to the clinical arena.