Peripheral End Research Articles

Lab-grown, 3D Extracellular Matrix Particles Improve Cardiac Function and Morphology in Myocardial Ischemia.

The promise of injection of extracellular matrix (ECM) from animal hearts as a treatment of myocardial ischemia has been limited by immune reactions and harsh ECM-damaging extraction procedures. We developed a novel method to produce lab-grown human 3D acellular ECM particles from human mesenchymal stem cells (MSCs) to mitigate product variability, immunogenicity, and preserve ECM architecture. We hypothesized that intramyocardial injection (I/M) of this novel ECM (dia ~200 microns) would improve cardiac function in a post-myocardial infarction (MI) murine model. WT mice aged 8-10 weeks underwent ligation of the LAD artery and I/M injection of 10 uL ECM or normal saline (n=10/group). Compared to control, ECM-treated hearts showed significant reduction in infarct size (p=0.04), increased capillary density in ischemic myocardium (p=0.01), and increased fractional shortening (FS) (p>0.05) on POD 14, 21, and 28 by echocardiography. There were no significant differences in immunogenic response as determined by TNF⍺, IL6, CD86, or CD163 levels (p>0.05 for all) in the hearts. Biodistribution of fluorophore-conjugated ECM demonstrated localized epifluorescence in the heart after I/M injection, without significant peripheral end organ epifluorescence. Proteomic analysis of ischemic and perfused myocardium from control and ECM-treated hearts using LC-MS/MS (n=3/group) detected significant changes in proteins involved in cardiomyocyte contractility and fatty acid metabolism. These findings suggest that 3D ECM particles induce recovery of ischemic myocardium, by upregulating protein networks involved in cellular contractility and metabolism. Taken together, 3D ECM particles represent a promising therapy for MI, and warrant confirmatory studies in a high-fidelity large animal model.

Higher Steroid Production in the Right Adrenal Gland Compared to the Left One in db/db Mice, a Model of Type 2 Diabetic Obesity.

Vertebrates exhibit a left-right asymmetry from the central structures to the peripheral paired endocrine organs. However, the asymmetries in paired endocrine glands and the pathological consequences of such asymmetries remain largely unknown. The adrenal gland constitutes a pair of peripheral end organs in the neuroendocrine system, responsible for producing steroid hormones under stimuli. In the present study, the lateralized asymmetry of left and right adrenal glands in leptin receptor-deficit db/db mice was investigated. First, a morphological and histological examination showed that adrenal mass and adrenal cortex volume in db/db mice were significantly higher than in non-diabetic control mice. Then, adrenal transcriptomic and serum metabolomic analyses were performed. Adrenal steroid profiling showed that the levels of corticosterone and aldosterone in the right adrenal gland of db/db mice were two times higher than in the left one. The expression of multiple genes related to adrenal regeneration and innervation in db/db mice was reduced in contrast to the increased steroid hormone secretion. Furthermore, an examination of morphogens in asymmetric adrenal development revealed a significant differential expression of Shh and its receptor gene Ptch1. In conclusion, the present study has provided evidence that a superior steroidogenesis exists in the right adrenal gland of db/db mice and suggested that Shh signaling may play an important role in asymmetric adrenal responses in type 2 diabetes and its complications.

Tuning Pyrrolo[3,2-b] pyrrole Core-based hole transport materials properties via Addition of fluorine for highly efficient and Stable planar perovskite solar cells

Hole-transport materials (HTM) play a crucial role in functioning perovskite solar cells (PSCs). In this research, we develop and synthesize two pyrrolo[3,2-b] pyrrole core (PP) based small molecular HTMs, FPPY and BPPY with/without (w/wo) fluorine (F) substitution on PP core that connected to the carbazole diphenylamine peripheral end groups, respectively. The F-substituted fused electron-rich pyrrole ring core greatly impacts FPPY molecular surface charge distribution, which contributes to higher hole extraction properties and excellent band alignment. Finally, FPPY-based PSCs obtain a best power conversion efficiency (PCE) of 24.3 %, significantly higher than BPPY (20.1 %). After aging 2000 h at ambient condition (25 °C, 30–50 % RH), the FPPY-based device still keeps over 87 % of its initial PCE.

Experience with Gore’s Block in Patients with Lower Lumbar Radiculopathy

Abstract Lower lumbar radiculopathy is one of the most common presentations in the pain clinic outpatient department (OPD). A thorough history, physical examination, neurological assessment, and imaging help in the diagnosis and management. The inability to identify the correct pain generator often causes a failure of treatment. Dr. Satishchandra Gore has proposed a new method for the diagnosis of affected lower lumbar nerve root (L5 and S1) at a peripheral level. His hypothesis is that in an inflamed nerve root, sodium channels are upregulated at both proximal and distal ends (central and peripheral). This results in tenderness at the distal peripheral end of the nerve on palpation. We can block the sodium channels at the distal portion of the same inflamed nerve, which may be able to abolish pain. This procedure is called “Gore’s Block” and the result is called “Gore’s sign.” We used this technique in 10 patients with suspected L5-S1 radiculopathy. Out of 10 patients, seven patients had pain relief after Gore’s block. These seven patients also responded well to a Caudal epidural steroid injection. Two patients did not have significant pain relief with Gore’s block and had poor responses to epidural steroid injections. One patient got therapeutic pain relief after Gore’s block, probably due to the natural resolution of the disease. Gore’s block is a simple, OPD procedure, helpful in diagnosing the level of nerve affection in lower lumbar radiculopathy. It is diagnostic and has a good correlation with epidural blocks. Whether it is therapeutic in nature needs to be further investigated.

Indirect measurement of process parameters in peripheral end milling based on acoustic emission signals

In machining, current methods for online estimation of cutting parameters heavily rely on piezoelectric dynamometers. Albeit their high precision, integration into industrial environments is limited due to high cost and practical machine mounting constraints. To address this challenge, this study presents an indirect measurement method of the cutting depths in peripheral milling based on acoustic emission sensors. The proposed method involves extracting time-based features from a tailor-made envelope of the acoustic emission signal, identifying transitions between cutting phases from its waveform, and using these features to estimate radial and axial depths of cut through a geometric model of the tool-workpiece contact zone. Experiments show that this method can achieve relative errors below 5% in measuring the depths of cut, approaching the precision levels of piezoelectric dynamometers. This suggests that acoustic emission is an alternative process variable, enriching the spectrum of monitoring systems traditionally dependent on the measurement of cutting forces.

Touch receptor end-organ innervation and function require sensory neuron expression of the transcription factor Meis2

Touch sensation is primarily encoded by mechanoreceptors, called low-threshold mechanoreceptors (LTMRs), with their cell bodies in the dorsal root ganglia. Because of their great diversity in terms of molecular signature, terminal endings morphology, and electrophysiological properties, mirroring the complexity of tactile experience, LTMRs are a model of choice to study the molecular cues differentially controlling neuronal diversification. While the transcriptional codes that define different LTMR subtypes have been extensively studied, the molecular players that participate in their late maturation and in particular in the striking diversity of their end-organ morphological specialization are largely unknown. Here we identified the TALE homeodomain transcription factor Meis2 as a key regulator of LTMRs target-field innervation in mice. Meis2 is specifically expressed in cutaneous LTMRs, and its expression depends on target-derived signals. While LTMRs lacking Meis2 survived and are normally specified, their end-organ innervations, electrophysiological properties, and transcriptome are differentially and markedly affected, resulting in impaired sensory-evoked behavioral responses. These data establish Meis2 as a major transcriptional regulator controlling the orderly formation of sensory neurons innervating peripheral end organs required for light touch.

Touch receptor end-organ innervation and function require sensory neuron expression of the transcription factor Meis2.

Touch sensation is primarily encoded by mechanoreceptors, called low-threshold mechanoreceptors (LTMRs), with their cell bodies in the dorsal root ganglia. Because of their great diversity in terms of molecular signature, terminal endings morphology, and electrophysiological properties, mirroring the complexity of tactile experience, LTMRs are a model of choice to study the molecular cues differentially controlling neuronal diversification. While the transcriptional codes that define different LTMR subtypes have been extensively studied, the molecular players that participate in their late maturation and in particular in the striking diversity of their end-organ morphological specialization are largely unknown. Here we identified the TALE homeodomain transcription factor Meis2 as a key regulator of LTMRs target-field innervation in mice. Meis2 is specifically expressed in cutaneous LTMRs, and its expression depends on target-derived signals. While LTMRs lacking Meis2 survived and are normally specified, their end-organ innervations, electrophysiological properties, and transcriptome are differentially and markedly affected, resulting in impaired sensory-evoked behavioral responses. These data establish Meis2 as a major transcriptional regulator controlling the orderly formation of sensory neurons innervating peripheral end organs required for light touch.

Thermosensation and TRP Channels.

Somatosensory neurons can sense external temperature by converting sensation of temperature information to neural activity via afferent input to the central nervous system. Various populations of somatosensory neurons have specialized gene expression, including expression of thermosensitive transient receptor potential (TRP) ion channels. Thermosensitive TRP channels are responsible for thermal transduction at the peripheral ends of somatosensory neurons and can sense a wide range of temperatures. Here we focus on several thermosensitive TRP channels including TRPV1, TRPV4, TRPM2, TRPM3, TRPM8, TRPC5, and TRPA1 in sensory neurons. TRPV3, TRPV4, and TRPC5 are also involved in somatosensation in nonneuronal cells and tissues. In particular, we discuss whether skin senses ambient temperatures through TRPV3 and TRPV4 activation in skin keratinocytes and the involvement of TRPM2 expressed by hypothalamic neurons in thermosensation in the brain.

Comparative assessment of methods of the operative treatment of facial nerve damage caused during cerebellopontine angle neurinoma and meningioma removals

The aim of this research paper is to point out the preconditions for facial nerve damage during CPA tumour removals and, in such cases, the appropriate choice of reconstructive surgery. Materials and methods. In Uzhhorod National University, during the period of 2008 to 2019, surgical treatment of 212 patients with neurinomas and meningiomas of the CPA has been carried out. We have analyzed the cases of 35 (16.5%) patients with intraoperative damage of the facial nerve. The mentioned 35 patients underwent appropriate clinical examinations during the post-operative period, which confirmed the facial nerve damage to one degree or another according to the House-Brackmann scale. The clinical signs manifested as full eyelid contact with slight effort and slight facial asymmetry during maximal effortful laughter. Slight synkinesias were noticeable, and there were no contractures until the expression of clinical signs corresponding to grade 6 - total nerve paralysis in 5 patients. Results. The research demonstrated that patients with neurinomas larger than 3 cm in size are 5 times more likely to undergo intraoperative damage to the facial nerve than patients with the same tumour but 3 cm or less in size and 5 times more likely than patients with meningiomas as a whole. In the group of patients aged 20-40, there were twice as many men; in the group aged 40-50, women predominated; among patients older than 50, there were equal numbers of men and women. Remote catamnesis was traced in 19 patients, and contact with the rest of the patients was lost due to the war. Among the interviewed patients, 58% of the anastomosis was performed in the first 3 months after the initial surgery, 21% - in 4-6 months, and 21% - in more than 12 months. The optimal timing of reinnervation after the initial surgery is the first 6 months after tumour removal. Сonclusions. Nerve damage is more common during the removal of neurinomas 4cm or bigger in size. Reinnervation is accomplished by anastomosing the central end of the hypoglossal or accessory nerves to the peripheral end of the facial nerve, and both procedures are equally effective. Reinnervation should be performed 2 to 3 months after confirming nerve injury, but no later than 6 months.

Asymmetries of Left and Right Adrenal Glands in Neural Innervation and Glucocorticoids Production.

The adrenal gland is paired peripheral end organs of the neuroendocrine system and is responsible for producing crucial stress hormones from its two functional compartments, the adrenal cortex, and the adrenal medulla under stimuli. Left-right asymmetry in vertebrates exists from the central nervous system to peripheral paired endocrine glands. The sided difference in the cerebral cortex is extensively investigated, while the knowledge of asymmetry of paired endocrine glands is still poor. The present study aims to investigate the asymmetries of bilateral adrenal glands, which play important roles in stress adaptation and energy homeostasis via steroid hormones produced from the distinct functional zones. Left and right adrenal glands from male C57BL/6J mice were initially histologically analyzed, and high-throughput RNA sequencing was then used to detect the gene transcriptional difference between left and right adrenal glands. Subsequently, the enrichment of functional pathways and ceRNA regulatory work was validated. The results demonstrated that the left adrenal gland had higher tissue mass and levels of energy expenditure, whereas the right adrenal gland appeared to be more potent in glucocorticoid secretion. Further analysis of adrenal stem/progenitor cell markers predicted that Shh signaling might play an important role in the left-right asymmetry of adrenal glands. Of the hub miRNAs, miRNA-466i-5p was identified in the left-right differential innervation of the adrenal glands. Therefore, the present study provides evidence that there are asymmetries between the left and right adrenal glands in glucocorticoid production and neural innervation, in which Shh signaling and miRNA-466i-5p play an important role.

Ուղեղիկ-կամրջային անկյան նորագոյացությունների հեռացման ժամանակ վնասված դիմային նյարդի վիրահատական բուժումը, տարբերակների համեմատական գնահատականը

The preoperative and surgical circumstances of nerve damage, the severity of damage, indications for reinnervation, method of execution, complications, and rate of reinnervation were studied in 35 patients. The best way to restore the facial nerve after intraoperative damage is reinnervation: positive dynamics can be noticed within the first 5 months. Nerve damage most often occurs when neurinomas measuring 4cm or larger are removed. Reinnervation is carried out by anastomosis of the central ends of the hypoglossal or accessory nerve with the peripheral end of the facial nerve, and they are equally effective. Reinnervation should be carried out 2 - 3 months after confirming nerve damage but within 6 months at the latest. The rate of nerve reinnervation is confirmed through clinical symptoms and ENMG. The best preventative measure for nerve preservation is early surgery for small tumors.

A comparative study of Ghanaian propolis extracts: Chemometric analysis of the chromatographic profile, antioxidant, and hypoglycemic potential and identification of active constituents

Diabetes is a disease characterized by high post-prandial glucose levels, which lead to other complications such as peripheral end organ damage. The use of enzyme inhibitors in the management of Type-2 diabetes ensure the control of blood glucose levels via the control of carbohydrate metabolism. The use of standard agents such as acarbose is associated with unwanted side effects hence the need to investigate other sources of antihyperglycemic agents. Propolis, a natural substance from bees, possesses diverse biological activities including antioxidant, antimicrobial and antidiabetic properties. However, the phytochemical content of propolis and its extracts may vary depending on the geographical area, the solvent of extraction and type of bees. This study represents the first attempt to compare different extracts of propolis from the same source in sub-Saharan Africa. In this study, the effect of solvent and source of Ghanaian propolis on parameters such as the total phenolic and flavonoid contents, chromatographic profile, antioxidant and α-amylase inhibitory effects were investigated with the aim of identifying and characterizing the most promising extract, which could be of direct or indirect benefit in the management of Type-2 diabetes.Combinations of water, ethanol-water and ethanol extracts were prepared from propolis from three regions. Phytochemical screening was performed on the extracts after which the Folin Ciocalteu method and aluminum chloride colorimetric assay were used to estimate the total phenolic and flavonoid contents respectively. Antioxidant potential of extracts was estimated using DPPH and phosphomolybdenum assays. In-vitro α-amylase inhibition assay was used to investigate hypoglycemic effect of the extracts. Statistical tools such as ANOVA, principal component analysis, hierarchical cluster analysis employed to determine sources of variations within the data obtained, to classify the extracts based on activity and to predict the most effective extract. This extract was then subjected to UHPLC-Q-TOF MS/MS and GC–MS techniques to characterize the constituents.Chemometric analysis of the data obtained showed that the variations in the data could be explained by both propolis source and extraction solvent. Though ethanol extracts generally contained more constituents, the more notable activities were in the ethanol-water extracts. The ethanol-water extract of Bono East propolis (EWBE) was the most potent DPPH radical scavenger (IC50 of 149.37 ± 2.90 µg/mL as compared to 116.60 ± 0.93 µg/mL GAE standard). It was also one of the three extracts which were more potent than acarbose (369.89 µg/mL) in the α-amylase inhibition assay. The predominant constituents from the LC-MS dereplication of EWBE were caffeic acid and flavonoid derivatives whilst 5,5-dimethyl-1-oxa-5 silacyclononanone-9 was the most significant active constituent identified through the GC–MS analysis. The identified constituents are known to have strong antioxidant and antidiabetic properties.The effects of source and solvent of extraction on the biological and physicochemical properties of propolis in Ghana have been quantified using statistical tools. The combined biological effects of propolis suggest a possible role in their usage in the management of type-2-diabetes and its related complications. Ethanol-water extracts were the most promising with EWBE showing the strongest antihyperglycemic activity. Such extracts represent leads towards further research into toxicity and formulation in order to develop safe and useful products for the management of type-2 diabetes.

Synthesis of dendritic urethane acrylates for fabricating a robust honeycomb-like structure acting for SERS detection

In this study, novel dendritic urethane acrylate polymers were developed for the fabrication of robust honeycomb-like surfaces after exposure to a UV-crosslinking process. Through iterative synthesis based on a highly selective intermediate of 4-isocyanate-4′-(3,3-dimethyl-2,4-dioxo-azetidine)-diphenylmethane, poly(urea/malonamide) dendrons bearing peripheral methyl methacrylate end groups with well-defined structures were realized. A coating solution was prepared by the combined use of 30–70 wt% UA dendron acting as dendritic diluents and dendritic UA copolymers acting as amphiphiles that can fabricate honeycomb-like surfaces via a breath figure self-assembly process using water droplets as templates. The resulting film can be cured under UV light to achieve a robust honeycomb-like structure with a hexagonal structure exhibiting solvent-resistant properties in ethanol. Consequently, this solvent-resistant porous array can act as a substrate for the detection of vanishingly low concentrations of analytes that are aqueous insoluble via surface-enhanced Raman scattering analysis.

Peripheral Vestibular System Involvement in Multiple Sclerosis and Associations with the Disease Severity

Introduction: Multiple sclerosis (MS) is an autoimmune disease that can affect balance, gait, and improve fall risk. The aim of this study was to investigate peripheral vestibular system involvement in MS and associations with the disease severity. Methods: Thirty-five adult patients with MS and 14 age- and gender-matched healthy controls were evaluated using video head impulse test (v-HIT), cervical vestibular evoked myogenic potential (c-VEMP), ocular vestibular evoked myogenic potentials (o-VEMPs), and sensory organization test (SOT) of computerized dynamic posturography (CDP). The results of both groups were compared, and association with EDSS scores was evaluated. Results: There was no significant difference between the groups regarding v-HIT and c-VEMP results (p > 0.05). There was no association of the v-HIT, c-VEMP, and o-VEMP results with EDSS scores (p > 0.05). There was no significant difference between the o-VEMP results of the groups (p > 0.05) except for N1-P1 amplitudes (p = 0.01). The amplitudes of N1-P1 were significantly lower in the patients compared to controls (p = 0.01). There was no significant difference between the SOT results of the groups (p > 0.05). However, significant differences were found within and between groups when the patients were categorized according to their EDSS scores with a cutoff point of 3 (p < 0.05). There were negative correlations between the EDSS scores and composite (r = −396, p = 0.02) and somatosensory (SOM) scores (r = −487, p = 0.04) of CDP in the MS group. Conclusion: Although central and peripheral balance-related systems are affected in MS, the impact of disease on the peripheral vestibular end organ is subtle. In particular, the v-HIT, which was mentioned previously as a detector of brainstem dysfunction could not be a reliable tool in the detection of brainstem pathologies in MS patients. The o-VEMP amplitudes may be affected in the early stages of the disease, possibly due to the crossed ventral tegmental tract, oculomotor nuclei, or interstitial nucleus of Cajal involvements. An EDSS score >3 seems a cutoff level indicating abnormalities in balance integration.

Associations of Bilateral Vestibulopathy With Cognition in Older Adults Matched With Healthy Controls for Hearing Status

Recent literature suggests there may be a significant effect of the vestibular system on cognition and visuospatial processing. Given the increasing prevalence of dementia and individuals at risk for it, exploring possible modifiable risk factors, including vestibular dysfunction, is vital. To explore the association of bilateral vestibulopathy (BV) with cognitive function in older adults, taking hearing status into account, and to explore multiple vestibular characteristics and their potential associations with cognition in patients with BV. This cross-sectional study assessed older adults (age 55-84 years) with diagnosed BV from a single center using baseline measurements from the Gehoor, Evenwicht en Cognitie (GECKO) study, an ongoing prospective longitudinal cohort study. Each participant was individually matched with a healthy control based on age, sex, and hearing performance. Data were analyzed in January 2022. The primary outcome measure was cognition, measured by the Repeatable Battery for the Assessment of Neuropsychological Status for Hearing-Impaired Individuals (RBANS-H). A total of 68 patients were assessed, including 34 patients with BV (mean [SD] age, 63.3 [6.0] years; 18 [53%] men) matched with 34 control individuals without BV. Overall, participants with BV had a clinically meaningful lower score on the RBANS-H total scale compared with those without BV (mean [SD] score, 98.62 [12.70] vs 105.91 [11.03]). This decline was most pronounced in the subdomains of immediate memory (mean [SD] score, 107.74 [10.66] vs 112.26 [10.66]), visuospatial cognition (mean [SD] score, 90.06 [13.34] vs 100.47 [13.91]), and attention (mean [SD] score, 94.79 [16.39] vs 102.06 [12.97]). There were no differences in language or delayed memory subdomains. Within the BV population, 1 vestibular parameter (the Performance-Oriented Mobility Assessment, in particular the balance subscale) was associated with lower cognitive scores (r32 = 0.51; 95% CI, 0.20 to 0.72; η2 = 0.26). Other vestibular parameters, including measurements of the peripheral vestibular end organ and questionnaires, showed no association. These findings suggest there was an association between vestibular loss and cognitive impairment. Further research on the causal mechanisms underlying this association and the possible impact of vestibular rehabilitation on cognition is needed.

Numerical simulation of edge effects in silicon hetero-junction solar cells

Photovoltaic characteristics in silicon hetero-junction solar cells are affected by the peripheral structure of the cell, and this is commonly referred to as the edge effect. We systematically investigated the edge effect on the photovoltaic characteristics of silicon hetero-junction solar cells by simulation. The effect strongly depends not only on the dimension of the periphery but also on the lifetime of the photo-generated carrier in crystalline Silicon (c-Si), the surface recombination velocity at the c-Si/a-Si:H interface, and the surface recombination velocity at the end of the c-Si wafer. Therefore, how these parameters affect the photovoltaic characteristics was simulated for three cases: (1) when a sufficiently large peripheral region passivated by a-Si:H is shielded from light, (2) when the length of the periphery is finite and the surface recombination of the photo-generated carriers at the peripheral end occurs, and (3) when the periphery is partially or entirely illuminated. Moreover, on the basis of the simulation technique developed, we proposed a new electrode configuration that is suitable for small area test cells with several cm2.

Legal Interpreting and Translanguaging: Contested Spaces in the Centre-Periphery Dynamic

Community or public-service interpreting is often institutionally perceived by service providers as being based on an ideological framing of languages as monolingual bounded resources, and the interpreting act as a bridge between two centric and separate linguistic regimes (LB – LA). However, this monolingualism is an ideological construct rather than a linguistic reality, the product of an historic, one nation one language myth, that is increasingly challenged by post-modern, superdiverse societies and their consequent multilingual realities on the ground. In particular, in today’s world the superdiversity of people within nation states, with multiple linguistic resources, has given rise to the increasingly visible phenomenon of ‘translanguaging’, a creative, dynamic and fluid sourcing of diverse linguistic repertoires in synchronic discourse. What was once only considered to be at the periphery has begun to challenge monolingual hegemony and establish its own centrality in public and private speech.&#x0D; Translanguaging is ‘multilingualism from below’ (Pennycook &amp; Otsuji 2015), coming as it almost inevitably always does from the peripheral end of the spectrum, typically in urban spaces where language practices are part and parcel of getting things done. But when this emerges in a legal context, in a court of law, how should legal interpreters respond? Drawing on preliminary research involving a cohort of court /legal interpreters in the UK[1], this article explores the problems this presents to monolingual bridging approaches and proposes potential future developments for the interpreting profession. A cohort of 6 professional public-service interpreters in the UK. The research drew on questionnaires and personal correspondence over a 6-month period.

Genetic dissection of novel myopathy models reveals a role of CapZα and Leiomodin 3 during myofibril elongation.

Myofibrils within skeletal muscle are composed of sarcomeres that generate force by contraction when their myosin-rich thick filaments slide past actin-based thin filaments. Although mutations in components of the sarcomere are a major cause of human disease, the highly complex process of sarcomere assembly is not fully understood. Current models of thin filament assembly highlight a central role for filament capping proteins, which can be divided into three protein families, each ascribed with separate roles in thin filament assembly. CapZ proteins have been shown to bind the Z-disc protein α-actinin to form an anchoring complex for thin filaments and actin polymerisation. Subsequent thin filaments extension dynamics are thought to be facilitated by Leiomodins (Lmods) and thin filament assembly is concluded by Tropomodulins (Tmods) that specifically cap the pointed end of thin filaments. To study thin filament assembly in vivo, single and compound loss-of-function zebrafish mutants within distinct classes of capping proteins were analysed. The generated lmod3- and capza1b-deficient zebrafish exhibited aspects of the pathology caused by variations in their human orthologs. Although loss of the analysed main capping proteins of the skeletal muscle, capza1b, capza1a, lmod3 and tmod4, resulted in sarcomere defects, residual organised sarcomeres were formed within the assessed mutants, indicating that these proteins are not essential for the initial myofibril assembly. Furthermore, detected similarity and location of myofibril defects, apparent at the peripheral ends of myofibres of both Lmod3- and CapZα-deficient mutants, suggest a function in longitudinal myofibril growth for both proteins, which is molecularly distinct to the function of Tmod4.

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GDNF to the rescue: GDNF delivery effects on motor neurons and nerves, and muscle re-innervation after peripheral nerve injuries.

Peripheral nerve injuries commonly occur due to trauma, like a traffic accident. Peripheral nerves get severed, causing motor neuron death and potential muscle atrophy. The current golden standard to treat peripheral nerve lesions, especially lesions with large (≥ 3 cm) nerve gaps, is the use of a nerve autograft or reimplantation in cases where nerve root avulsions occur. If not tended early, degeneration of motor neurons and loss of axon regeneration can occur, leading to loss of function. Although surgical procedures exist, patients often do not fully recover, and quality of life deteriorates. Peripheral nerves have limited regeneration, and it is usually mediated by Schwann cells and neurotrophic factors, like glial cell line-derived neurotrophic factor, as seen in Wallerian degeneration. Glial cell line-derived neurotrophic factor is a neurotrophic factor known to promote motor neuron survival and neurite outgrowth. Glial cell line-derived neurotrophic factor is upregulated in different forms of nerve injuries like axotomy, sciatic nerve crush, and compression, thus creating great interest to explore this protein as a potential treatment for peripheral nerve injuries. Exogenous glial cell line-derived neurotrophic factor has shown positive effects in regeneration and functional recovery when applied in experimental models of peripheral nerve injuries. In this review, we discuss the mechanism of repair provided by Schwann cells and upregulation of glial cell line-derived neurotrophic factor, the latest findings on the effects of glial cell line-derived neurotrophic factor in different types of peripheral nerve injuries, delivery systems, and complementary treatments (electrical muscle stimulation and exercise). Understanding and overcoming the challenges of proper timing and glial cell line-derived neurotrophic factor delivery is paramount to creating novel treatments to tend to peripheral nerve injuries to improve patients’ quality of life.