The seventh blind test of crystal structure prediction: structure generation methods.

A seventh blind test of crystal structure prediction was organized by the Cambridge Crystallographic Data Centre featuring seven target systems of varying complexity: a silicon and iodine-containing molecule, a copper coordination complex, a near-rigid molecule, a cocrystal, a polymorphic small agrochemical, a highly flexible polymorphic drug candidate, and a polymorphic morpholine salt. In this first of two parts focusing on structure generation methods, many crystal structure prediction (CSP) methods performed well for the small but flexible agrochemical compound, successfully reproducing the experimentally observed crystal structures, while few groups were successful for the systems of higher complexity. A powder X-ray diffraction (PXRD) assisted exercise demonstrated the use of CSP in successfully determining a crystal structure from a low-quality PXRD pattern.

Insights into the spectrum of transtibial prosthetic socket design from expert clinicians and their digital records.

Background: Transtibial prosthetic sockets are often grouped into patella tendon bearing (PTB) or total surface bearing (TSB) designs, but many variations in rectifications are used to apply these principles to an individual's personalised socket. Prosthetists currently have little objective evidence to assist them as they make design choices.

Aims: To compare rectifications made by experienced prosthetists across a range of patient demographics and limb shapes to improve understanding of socket design strategies.

Bolstering the Measurement of Racial Inequity of COVID-19 Vaccine Uptake.

Inequities in COVID-19 vaccine uptake by racialized groups have been persistent throughout the vaccine rollout, leading to disparate burdens of COVID-19 outcomes. A cross-sectional study was conducted to determine COVID-19 vaccine uptake across racialized groups within the nine-county Finger Lakes region of New York State in December 2021. Cross-matching and validation were performed across multiple health information systems for the region to reduce the percentage of vaccine records with missing race information.

Evaluation of the difficult intravenous access (DIVA) scoring in hospitalized pediatric patients.

Highlights: The DIVA scoring tool has previously been validated in the pediatric ED setting. Our project applied DIVA to an inpatient pediatric sample. DIVA may not predict likelihood of PIV success in the inpatient setting.

Pooled image-base screening of mitochondria with microraft isolation distinguishes pathogenic mitofusin 2 mutations.

Most human genetic variation is classified as variants of uncertain significance. While advances in genome editing have allowed innovation in pooled screening platforms, many screens deal with relatively simple readouts (viability, fluorescence) and cannot identify the complex cellular phenotypes that underlie most human diseases. In this paper, we present a generalizable functional genomics platform that combines high-content imaging, machine learning, and microraft isolation in a method termed "Raft-Seq".

Changes in Tissue Composition and Load Response After Transtibial Amputation Indicate Biomechanical Adaptation.

Despite the potential for biomechanical conditioning with prosthetic use, the soft tissues of residual limbs following lower-limb amputation are vulnerable to damage. Imaging studies revealing morphological changes in these soft tissues have not distinguished between superficial and intramuscular adipose distribution, despite the recognition that intramuscular fat levels indicate reduced tolerance to mechanical loading. Furthermore, it is unclear how these changes may alter tissue tone and stiffness, which are key features in prosthetic socket design.

Single-cell RNA sequencing reveals the induction of novel myeloid and myeloid-associated cell populations in visceral fat with long-term obesity.

Macrophages and other immune cells are important contributors to obesity-associated inflammation; however, the cellular identities of these specific populations remain unknown. In this study, we identified individual populations of myeloid cells found in mouse epididymal/visceral adipose tissue by single-cell RNA sequencing, immunofluorescence, and flow cytometry. Multiple canonical correlation analysis identified 11 unique myeloid and myeloid-associate cell populations.

Domain-centric database to uncover structure of minimally characterized viral genomes.

Protein domain-based approaches to analyzing sequence data are valuable tools for examining and exploring genomic architecture across genomes of different organisms. Here, we present a complete dataset of domains from the publicly available sequence data of 9,051 reference viral genomes. The data provided contain information such as sequence position and neighboring domains from 30,947 pHMM-identified domains from each reference viral genome.

Planning and Analysis of Axon Degeneration Screening Experiments.

A network of intersecting molecular pathways interacts to initiate and execute axon destruction. Maximum protection against axon degeneration likely requires more than manipulation of a single target. Here, we describe the process of designing a high-throughput arrayed screening assay for the identification of key factors responsible for axon destruction and/or protection.

Establishing a measurement array to assess tissue tolerance during loading representative of prosthetic use.

Background: In the early stages of rehabilitation after primary amputation, residual limb soft tissues have not been mechanically conditioned to support load and are vulnerable to damage from prosthetic use. There is limited quantitative knowledge of skin and soft tissue response to prosthetic loading.

Methods: An in-vivo protocol was developed to establish suitable measures to assess tissue tolerance during loading representative of early prosthesis use.

A Three-Dimensional Cell Culture System To Model RNA Virus Infections at the Blood-Brain Barrier.

The blood-brain barrier (BBB) comprises the foremost protective barrier in the brain and is composed in part of a layer of microvascular endothelial cells that line the capillaries surrounding the brain. Here, we describe a human three-dimensional (3-D) cell-based model of the BBB microvascular endothelium that recapitulates properties of these cells , including physiologically relevant transcriptional profiles, the capacity to induce potent antimicrobial innate immune signaling, and the ability to resist infection by diverse RNA viruses, including members of the enterovirus (coxsackievirus B, echovirus 11, enterovirus 71, poliovirus) and flavivirus (dengue virus, Zika virus [ZIKV]) families. We show that disruption of apical tight junctions by proinflammatory cytokine tumor necrosis factor alpha (TNF-α) sensitizes 3-D-cultured BBB cells to ZIKV infection and that 3-D derived BBB cells can be used to model the transmigration of ZIKV-infected monocytes across the endothelial barrier to access underlying astrocytes.

Avian axons undergo Wallerian degeneration after injury and stress.

The integrity of long axons is essential for neural communication. Unfortunately, relatively minor stress to a neuron can cause extensive loss of this integrity. Axon degeneration is the cell-intrinsic program that actively deconstructs an axon after injury or damage.

Type III Interferons Produced by Human Placental Trophoblasts Confer Protection against Zika Virus Infection.

During mammalian pregnancy, the placenta acts as a barrier between the maternal and fetal compartments. The recently observed association between Zika virus (ZIKV) infection during human pregnancy and fetal microcephaly and other anomalies suggests that ZIKV may bypass the placenta to reach the fetus. This led us to investigate ZIKV infection of primary human trophoblasts (PHTs), which are the barrier cells of the placenta.

Altered entrainment to the day/night cycle attenuates the daily rise in circulating corticosterone in the mouse.

The suprachiasmatic nucleus (SCN) is a circadian oscillator entrained to the day/night cycle via input from the retina. Serotonin (5-HT) afferents to the SCN modulate retinal signals via activation of 5-HT1B receptors, decreasing responsiveness to light. Consequently, 5-HT1B receptor knockout (KO) mice entrain to the day/night cycle with delayed activity onsets.

Nitric oxide mediates activity-dependent plasticity of retinal bipolar cell output via S-nitrosylation.

Coding a wide range of light intensities in natural scenes poses a challenge for the retina: adaptation to bright light should not compromise sensitivity to dim light. Here we report a novel form of activity-dependent synaptic plasticity, specifically, a "weighted potentiation" that selectively increases output of Mb-type bipolar cells in the goldfish retina in response to weak inputs but leaves the input-output ratio for strong stimuli unaffected. In retinal slice preparation, strong depolarization of bipolar terminals significantly lowered the threshold for calcium spike initiation, which originated from a shift in activation of voltage-gated calcium currents (ICa) to more negative potentials.

Small-molecule antagonists of melanopsin-mediated phototransduction.

Melanopsin, expressed in a subset of retinal ganglion cells, mediates behavioral adaptation to ambient light and other non-image-forming photic responses. This has raised the possibility that pharmacological manipulation of melanopsin can modulate several central nervous system responses, including photophobia, sleep, circadian rhythms and neuroendocrine function. Here we describe the identification of a potent synthetic melanopsin antagonist with in vivo activity.

Carbenoxolone blocks the light-evoked rise in intracellular calcium in isolated melanopsin ganglion cell photoreceptors.

Background: Retinal ganglion cells expressing the photopigment melanopsin are intrinsically photosensitive (ipRGCs). These ganglion cell photoreceptors send axons to several central targets involved in a variety of functions. Within the retina ipRGCs provide excitatory drive to dopaminergic amacrine cells via glutamatergic signals and ipRGCs are coupled to wide-field GABAergic amacrine cells via gap junctions.

Light-evoked calcium responses of isolated melanopsin-expressing retinal ganglion cells.

A small number (<2%) of mammalian retinal ganglion cells express the photopigment melanopsin and are intrinsically photosensitive (ipRGCs). Light depolarizes ipRGCs and increases intracellular calcium levels ([Ca2+]i) but the signaling cascades underlying these responses have yet to be elucidated. To facilitate physiological studies on these rare photoreceptors, highly enriched ipRGC cultures from neonatal rats were generated using anti-melanopsin-mediated plate adhesion (immunopanning).

5-HT1B receptor-mediated presynaptic inhibition of GABA release in the suprachiasmatic nucleus.

The suprachiasmatic nucleus (SCN) receives a dense serotonergic innervation that modulates photic input to the SCN via serotonin 1B (5-HT1B) presynaptic receptors on retinal glutamatergic terminals. However, the majority of 5-HT1B binding sites in the SCN are located on nonretinal terminals and most axonal terminals in the SCN are GABAergic. We therefore tested the hypothesis that 5-HT1B receptors might also be located on SCN GABAergic terminals by examining the effects of the highly selective 5-HT1B receptor agonist CP-93,129 on SCN miniature inhibitory postsynaptic currents (mIPSCs).

Determinants of universal adolescent hepatitis B vaccine uptake.

The UK is currently considering the introduction of universal hepatitis B vaccination. This study of determinants of vaccine uptake among school based adolescents shows that living in areas of high deprivation, commonly associated with injecting drug risk behaviours, was the most important factor, with statistically significant lower odds of receiving three doses. This was less pronounced for receipt of two doses.

UK guidelines for use of erythromycin chemoprophylaxis in persons exposed to pertussis.

Pertussis is well controlled in the UK as a result of an effective vaccination programme. Nevertheless, the disease has not been eliminated, and cases still occur in the most vulnerable group of young infants. Erythromycin chemoprophylaxis has been advocated for use in contacts to prevent secondary cases but the evidence for its use is weak.

Universal hepatitis B vaccination of UK adolescents: a feasibility and acceptability study.

The feasibility of introducing universal hepatitis B immunisation was assessed by offering the vaccine to all 11-12 year old pupils in Greater Glasgow (approximately 10,800). Consent was received from 92% of the school roll, and 91.3%, 89.

Mortality of mental health service recipients in Vermont and Oklahoma.

The authors compared statewide mortality rates for people with severe mental illness who were served in public mental health systems of care in Vermont and Oklahoma. In both states, mortality rates for younger service recipients, but not for older recipients, were significantly higher than those for the general population. In interpreting cross-region comparisons, several possible causes of variation, including differences in caseload composition and causes outside the control of the public mental health authority, must be considered.