Acute and Chronic Effects of Static Stretching on Intramuscular Hamstring Stiffness.

Passive hamstring stiffness varies proximo-distally, resulting in inhomogeneous tissue strain during stretching that may affect localized adaptations and risk of muscle injuries. The purpose of the present study was to determine the acute and chronic effects of static stretching (SS) on intramuscular hamstring stiffness. Thirty healthy active participants had acute changes in passive biceps femoris (BF), semimembranosus (SM), and semitendinosus (ST) stiffness measured at 25% (proximal), 50% (middle), and 75% (distal) muscle length, using shear-wave elastography, immediately after SS. Participants then completed 4 weeks of either a SS intervention (n = 15) or no intervention (CON, n = 15) with stiffness measured before and after the interventions. The acute and chronic effects of SS were compared between anatomical regions and between regions on the basis of their relative stiffness pre-intervention. Acutely, SS decreased stiffness throughout the BF and SM (p ≤ 0.05) but not the ST (p = 0.326). However, a regional effect of stretching was observed for SM and ST with greater reduction in stiffness occurring in stiffer muscular regions (p = 0.001-0.013). Chronically, SS increased BF and ST (p < 0.05), but not SM (p = 0.422) stiffness compared with CON, but no regional effect of stretching was observed in any muscle (p = 0.361-0.833). SS resulted in contrasting acute and chronic effects, acutely decreasing stiffness in stiffer regions while chronically increasing stiffness. These results indicate that the acute effects of SS vary along the muscle's length on the basis of the relative stiffness of the muscle and that acute changes in stiffness from SS are unrelated to chronic adaptations.

Outcome of tenoscopically guided palmar/plantar annular ligament desmotomy for the treatment of palmar/plantar annular ligament constriction without concurrent intrathecal soft-tissue injury in a UK horse population.

OBJECTIVE: To determine the outcome of tenoscopically guided palmar/plantar annular ligament (PAL) desmotomy to treat PAL constriction without concurrent intrathecal soft-tissue injury, notably of the digital flexor tendons and manica flexoria. STUDY DESIGN: Retrospective multicenter cohort study. ANIMALS: Sixty-five horses. METHODS: Horses from four UK equine hospitals, with digital flexor tendon sheath (DFTS) tenosynovitis, which underwent tenoscopically guided PAL desmotomy for treatment of PAL constriction between 2017 and 2022 were included. All horses had lameness isolated to the DFTS/PAL, and PAL constriction was diagnosed tenoscopically when there was difficulty maneuvering the endoscope into or through the fetlock canal. Horses with tearing of the digital flexor tendons and/or manica flexoria, or any other intrathecal pathology, were excluded. Follow up was via structured telephone questionnaire. RESULTS: Follow up (median 25 months) was available for 61 horses with cobs and ponies predominating. Forty-two returned to their previous level of work, or a higher level, postoperatively and 50 owners were satisfied with the outcome of surgery. Eleven horses returned to lower level exercise, and six were retired/euthanized as they did not regain soundness. Fifty-two horses achieved soundness (median 3 months postoperatively). CONCLUSION: Tenoscopically guided PAL desmotomy for the treatment of PAL constriction in the absence of intrathecal soft tissue injury had a good prognosis for return to previous levels of exercise in a UK horse population. CLINICAL SIGNIFICANCE: The prognosis for horses undergoing tenoscopically guided PAL desmotomy to treat PAL constriction in the absence of intrathecal injury is better than previously described. Cobs and ponies seem to be predisposed to PAL constriction in agreement with the previous literature.

Covalent hitchhikers guide proteins to the nucleus.

In this issue of Cell Chemical Biology, Peng and Weerapana1 report the combination of chemoproteomic and proximity-based labeling approaches to identify cysteines in nuclear proteins that are reactive toward electrophilic probe compounds. They apply this novel technology to identify proteins that are localized to the nucleus and chromatin upon probe labeling.

ROS-induced ribosome impairment underlies ZAKα-mediated metabolic decline in obesity and aging.

The ribotoxic stress response (RSR) is a signaling pathway in which the p38- and c-Jun N-terminal kinase (JNK)-activating mitogen-activated protein kinase kinase kinase (MAP3K) ZAKα senses stalling and/or collision of ribosomes. Here, we show that reactive oxygen species (ROS)-generating agents trigger ribosomal impairment and ZAKα activation. Conversely, zebrafish larvae deficient for ZAKα are protected from ROS-induced pathology. Livers of mice fed a ROS-generating diet exhibit ZAKα-activating changes in ribosomal elongation dynamics. Highlighting a role for the RSR in metabolic regulation, ZAK-knockout mice are protected from developing high-fat high-sugar (HFHS) diet-induced blood glucose intolerance and liver steatosis. Finally, ZAK ablation slows animals from developing the hallmarks of metabolic aging. Our work highlights ROS-induced ribosomal impairment as a physiological activation signal for ZAKα that underlies metabolic adaptation in obesity and aging.

Stimulus-Induced Relief of Intentionally Incorporated Frustration Drives Refolding of a Water-Soluble Biomimetic Foldamer.

Frustrated, or nonoptimal, interactions have been proposed to be essential to a protein's ability to display responsive behavior such as allostery, conformational signaling, and signal transduction. However, the intentional incorporation of frustrated noncovalent interactions has not been explored as a design element in the field of dynamic foldamers. Here, we report the design, synthesis, characterization, and molecular dynamics simulations of the first dynamic water-soluble foldamer that, in response to a stimulus, exploits relief of frustration in its noncovalent network to structurally rearrange from a pleated to an intercalated columnar structure. Thus, relief of frustration provides the energetic driving force for structural rearrangement. This work represents a previously unexplored design element for the development of stimulus-responsive systems that has potential application to materials chemistry, synthetic biology, and molecular machines.

The Presence of Two MyoD Genes in a Subset of Acanthopterygii Fish Is Associated with a Polyserine Insert in MyoD1.

The MyoD gene was duplicated during the teleost whole genome duplication and, while a second MyoD gene (MyoD2) was subsequently lost from the genomes of some lineages (including zebrafish), many fish lineages (including Alcolapia species) have retained both MyoD paralogues. Here we reveal the expression patterns of the two MyoD genes in Oreochromis (Alcolapia) alcalica using in situ hybridisation. We report our analysis of MyoD1 and MyoD2 protein sequences from 54 teleost species, and show that O. alcalica, along with some other teleosts, include a polyserine repeat between the amino terminal transactivation domains (TAD) and the cysteine-histidine rich region (H/C) in MyoD1. The evolutionary history of MyoD1 and MyoD2 is compared to the presence of this polyserine region using phylogenetics, and its functional relevance is tested using overexpression in a heterologous system to investigate subcellular localisation, stability, and activity of MyoD proteins that include and do not include the polyserine region.

Domestic violence and abuse in local child safeguarding policy: How is the problem represented?

Within the United Kingdom, domestic violence and abuse (DVA) is the most commonly identified factor within child in need assessments, with rates increasing in recent years in addition to 'lockdown'-related spikes. This article examines the representation of DVA in local child safeguarding policies using Bacchi's (2009) 'What is the problem represented to be?' approach. Policies were collected from the websites of all the child safeguarding partnerships of England in July 2021. In total, we identified 59 policies. These policies are designed to guide local responses to DVA across services and thus have potential for substantial impact on practice across health and social care. Our results suggest that local DVA policy in England exists within a conceptual framework which spotlights the individual and lacks attention to their context. We argue that these policies focus on adults, neglecting attention to children within their own safeguarding policies. This is through children being peripheralized within the conceptualisation of 'victim' and the assessed adult risk being used as a proxy measure for the risk to child. Demographic discussions build an image of DVA as an issue that can affect anyone, but with little acknowledgement of the vulnerabilities facing proportions of the population and their complexities - when such vulnerabilities are discussed, they are individualised and viewed in absence of their societal causes, potentially eclipsing critical elements of a child's experience of DVA. The implications of our results are wide-ranging but suggest a need to refocus on children and their context within local DVA policy.

Genomic Characterization of the Cluster CZ4 Gordonia terrae Phage Oregano.

Oregano is a novel cluster CZ4 bacteriophage isolated from the soil using the bacterial host Gordonia terrae. The Oregano genome is 47,575 bp long and encodes two tyrosine integrases and a toxin/antitoxin system. It shares an immunity repressor with both Gordonia and Mycobacterium phages that spans 7 clusters.

Direct Compaction Drug Product Process Modeling.

Most challenges during the development of solid dosage forms are related to the impact of any variations in raw material properties, batch size, or equipment scales on the product quality and the control of the manufacturing process. With the ever pertinent restrictions on time and resource availability versus heightened expectations to develop, optimize, and troubleshoot manufacturing processes, targeted and robust science-based process modeling platforms are essential. This review focuses on the modeling of unit operations and practices involved in batch manufacturing of solid dosage forms by direct compaction. An effort is made to highlight the key advances in the past five years, and to propose potentially beneficial future study directions.

Highlighting DEM's Potential to Gauge Mechanistic Attributes of MUPS Tablet and Capsule Formulations.

Simulation of pharmaceutical unit operations by the discrete element method (DEM) has elevated our understanding of the impact of single-particle interactions on themselves, and on the entire tablets/powder. Studies in the past have shown how this knowledge helps to mitigate/solve multiple challenges during conventional formulation and process development/modernization/troubleshooting, with minimal use of active drug material. This communication adds to this- highlighting the tool's potential for a rapid preliminary assessment of the mechanistic attributes of multiple unit particle system (MUPS) based tablet and capsule drug products.

Ultrasonographic guidance for perineural injections of the cervical spinal nerves in horses.

OBJECTIVE: To evaluate the accuracy of ultrasonographic guidance for injection near the ventral rami of the cervical spinal nerves (VRCSN). STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Ten cadavers (n = 40 injections). METHODS: Left and right VRCSN at C4/5 and C5/6 were infiltrated at the intervertebral foramen (IVF) under ultrasonographic guidance. A vertically orientated 3.5-MHz curvilinear probe was used to identify the craniocaudal midpoint of the articular process joint (APJ). The probe was moved ventrally until the IVF was identified. An 18-gauge 15-cm-long spinal needle was aimed immediately below the ventral margin of the cranial articular process, where 1 mL of latex was injected. Cadavers were dissected, and the location of the latex was recorded relative to the ventral ramus, the spinal cord, and the vertebral artery. RESULTS: Direct infiltration of the ventral ramus occurred in 73% (29/40) of injections; 15% (6/40) of injections were < 0.5 cm from the ventral ramus, and 13% (5/40) of injections were > 0.5 cm (maximum 1.5 cm). Latex was located at a mean of 2.4 cm (range, 0.8-4) from the spinal cord and 0.9 cm (range, 0-1.5) from the vertebral artery. CONCLUSION: Ultrasonographic guidance of perineural injections of the caudal VRCSN was repeatable and accurate, with 88% of injections located within 0.5 cm of the ventral ramus. Iatrogenic damage was limited to one penetration into the vertebral artery. CLINICAL SIGNIFICANCE: Ultrasonographic guidance of perineural injections of the caudal VRCSN may be considered by operators experienced in cervical APJ scanning in horses with suspected cervical spinal nerve compression.

Natural ultraviolet radiation exposure alters photosynthetic biology and improves recovery from desiccation in a desert moss.

Plants in dryland ecosystems experience extreme daily and seasonal fluctuations in light, temperature, and water availability. We used an in situ field experiment to uncover the effects of natural and reduced levels of ultraviolet radiation (UV) on maximum PSII quantum efficiency (Fv/Fm), relative abundance of photosynthetic pigments and antioxidants, and the transcriptome in the desiccation-tolerant desert moss Syntrichia caninervis. We tested the hypotheses that: (i) S. caninervis plants undergo sustained thermal quenching of light [non-photochemical quenching (NPQ)] while desiccated and after rehydration; (ii) a reduction of UV will result in improved recovery of Fv/Fm; but (iii) 1 year of UV removal will de-harden plants and increase vulnerability to UV damage, indicated by a reduction in Fv/Fm. All field-collected plants had extremely low Fv/Fm after initial rehydration but recovered over 8 d in lab-simulated winter conditions. UV-filtered plants had lower Fv/Fm during recovery, higher concentrations of photoprotective pigments and antioxidants such as zeaxanthin and tocopherols, and lower concentrations of neoxanthin and Chl b than plants exposed to near natural UV levels. Field-grown S. caninervis underwent sustained NPQ that took days to relax and for efficient photosynthesis to resume. Reduction of solar UV radiation adversely affected recovery of Fv/Fm following rehydration.

Fusing Location Data for Depression Prediction.

Recent studies have demonstrated that geographic location features collected using smartphones can be a powerful predictor for depression. While location information can be conveniently gathered by GPS, typical datasets suffer from significant periods of missing data due to various factors (e.g., phone power dynamics, limitations of GPS). A common approach is to remove the time periods with significant missing data before data analysis. In this paper, we develop an approach that fuses location data collected from two sources: GPS and WiFi association records, on smartphones, and evaluate its performance using a dataset collected from 79 college students. Our evaluation demonstrates that our data fusion approach leads to significantly more complete data. In addition, the features extracted from the more complete data present stronger correlation with self-report depression scores, and lead to depression prediction with much higher F 1 scores (up to 0.76 compared to 0.5 before data fusion). We further investigate the scenerio when including an additional data source, i.e., the data collected from a WiFi network infrastructure. Our results show that, while the additional data source leads to even more complete data, the resultant F 1 scores are similar to those when only using the location data (i.e., GPS and WiFi association records) from the phones.

Automatic Depression Prediction Using Internet Traffic Characteristics on Smartphones.

Depression is a serious mental health problem. Recently, researchers have proposed novel approaches that use sensing data collected passively on smartphones for automatic depression screening. While these studies have explored several types of sensing data (e.g., location, activity, conversation), none of them has leveraged Internet traffic of smartphones, which can be collected with little energy consumption and the data is insensitive to phone hardware. In this paper, we explore using coarse-grained meta-data of Internet traffic on smartphones for depression screening. We develop techniques to identify Internet usage sessions (i.e., time periods when a user is online) and extract a novel set of features based on usage sessions from the Internet traffic meta-data. Our results demonstrate that Internet usage features can reflect the different behavioral characteristics between depressed and non-depressed participants, confirming findings in psychological sciences, which have relied on surveys or questionnaires instead of real Internet traffic as in our study. Furthermore, we develop machine learning based prediction models that use these features to predict depression. Our evaluation shows that Internet usage features can be used for effective depression prediction, leading to F 1 score as high as 0.80.

Grant Report on SCH: Personalized Depression Treatment Supported by Mobile Sensor Analytics.

We report on the newly started project "SCH: Personalized Depression Treatment Supported by Mobile Sensor Analytics". The current best practice guidelines for treating depression call for close monitoring of patients, and periodically adjusting treatment as needed. This project will advance personalized depression treatment by developing a system, DepWatch, that leverages mobile health technologies and machine learning tools. The objective of DepWatch is to assist clinicians with their decision making process in the management of depression. The project comprises two studies. Phase I collects sensory data and other data, e.g., clinical data, ecological momentary assessments (EMA), tolerability and safety data from 250 adult participants with unstable depression symptomatology initiating depression treatment. The data thus collected will be used to develop and validate assessment and prediction models, which will be incorporated into DepWatch system. In Phase II, three clinicians will use DepWatch to support their clinical decision making process. A total of 128 participants under treatment by the three participating clinicians will be recruited for the study. A number of new machine learning techniques will be developed.

Mechanics of Pharmaceutical Pellets-Constitutive Properties, Deformation, and Breakage Behavior.

To ensure robust manufacturing of unit-based oral solid dosage forms with minimal structural imperfections and high mechanical reliability across subsequent processing unit operations (e.g., withstanding mechanical stresses during coating, optional axial compression, handling, packaging, storage, and transport conditions), process design should include consideration of precise limits of accurate micro, macro, and bulk properties of the constituent pellets. This communication presents a comprehensive intricate database of micromechanical properties' and breakage probability distribution functions of pellets, illustrating the stiffening and strengthening effects of coatings and the softening and weakening effects of structural moisture. Further insights such as the (contact) history-dependent softening during decompression, strain hardening on repeated stressing, strength recovery by drying, and the fragmentation pattern by cracking are also presented. The contents herein are based on conveniently performable lab-scale diametrical compression measurements on model microcrystalline cellulose pellets-demonstrating feasibility of the approach and validity of the contribution.

Single cell analysis reveals the stochastic phase of reprogramming to pluripotency is an ordered probabilistic process.

Despite years of research, the reprogramming of human somatic cells to pluripotency remains a slow, inefficient process, and a detailed mechanistic understanding of reprogramming remains elusive. Current models suggest reprogramming to pluripotency occurs in two-phases: a prolonged stochastic phase followed by a rapid deterministic phase. In this paradigm, the early stochastic phase is marked by the random and gradual expression of pluripotency genes and is thought to be a major rate-limiting step in the successful generation of induced Pluripotent Stem Cells (iPSCs). Recent evidence suggests that the epigenetic landscape of the somatic cell is gradually reset during a period known as the stochastic phase, but it is known neither how this occurs nor what rate-limiting steps control progress through the stochastic phase. A precise understanding of gene expression dynamics in the stochastic phase is required in order to answer these questions. Moreover, a precise model of this complex process will enable the measurement and mechanistic dissection of treatments that enhance the rate or efficiency of reprogramming to pluripotency. Here we use single-cell transcript profiling, FACS and mathematical modeling to show that the stochastic phase is an ordered probabilistic process with independent gene-specific dynamics. We also show that partially reprogrammed cells infected with OSKM follow two trajectories: a productive trajectory toward increasingly ESC-like expression profiles or an alternative trajectory leading away from both the fibroblast and ESC state. These two pathways are distinguished by the coordinated expression of a small group of chromatin modifiers in the productive trajectory, supporting the notion that chromatin remodeling is essential for successful reprogramming. These are the first results to show that the stochastic phase of reprogramming in human fibroblasts is an ordered, probabilistic process with gene-specific dynamics and to provide a precise mathematical framework describing the dynamics of pluripotency gene expression during reprogramming by OSKM.

Separation behavior of short single- and double-stranded DNA in 1 micron and 100 nm glass channels.

Micro- and nanofluidic lab-on-chip technology offers the unique capability of high-resolution separation, identification, and manipulation of biomolecules with broad applications in chemistry, biology, and medicine. In this work, we probe the effects of ionic strength on separation of ss- and dsDNA within 1 micron and 100 nm-deep glass channels. Separation behavior of DNA is influenced by a number of parameters, including ionic strength, melting temperature, strand length, strand conformation, and channel size. Specifically, we find a shift in the observed mobility of 10-bp (base pair) dsDNA for different ionic strengths due to changes in kinetic parameters, underlying the importance of these considerations when working with short DNA. For 50-base DNA, the electrophoretic mobility difference between ss- and dsDNA increases as the ionic strength increases due to changes in conformation of the ssDNA. Finally, we find that decreasing channel size decreases the absolute electrophoretic mobility of 10- and 20-bp ss- and dsDNA, due to both hydrodyamic confinement and electric double layer (EDL) interactions. We hypothesize that about 4% mobility reduction is due to hydrodynamic confinement, which is observed at all ionic strengths, and further reduction is due to EDL interactions between the DNA and the channel walls, only observed at low ionic strengths.

A model of proto-object based saliency.

Organisms use the process of selective attention to optimally allocate their computational resources to the instantaneously most relevant subsets of a visual scene, ensuring that they can parse the scene in real time. Many models of bottom-up attentional selection assume that elementary image features, like intensity, color and orientation, attract attention. Gestalt psychologists, however, argue that humans perceive whole objects before they analyze individual features. This is supported by recent psychophysical studies that show that objects predict eye-fixations better than features. In this report we present a neurally inspired algorithm of object based, bottom-up attention. The model rivals the performance of state of the art non-biologically plausible feature based algorithms (and outperforms biologically plausible feature based algorithms) in its ability to predict perceptual saliency (eye fixations and subjective interest points) in natural scenes. The model achieves this by computing saliency as a function of proto-objects that establish the perceptual organization of the scene. All computational mechanisms of the algorithm have direct neural correlates, and our results provide evidence for the interface theory of attention.