Biology subjects

Hassan, A. S.

Publications and source records attributed to Hassan, A. S..

4 recordsLinked to original sources

bioRxiv2021

Estimates of persistent inward currents are reduced in upper limb motor units of older adults

Aging is a natural process that causes alterations in the neuromuscular system, which contribute to weakness and reduced quality of life. Reduced firing rates of individual motor units (MUs) likely contribute to weakness, but the mechanisms underlying reduced firing rates are not clear. Persistent inward currents (PICs) are crucial for the initiation, gain control, and maintenance of motoneuron firing, and are directly proportional to the level of monoaminergic input. Since the concentration of monoamines (i.e. serotonin and norepinephrine) are reduced with age, we sought to determine if estimates of PICs are reduced in older (>60 years old) compared to younger adults (<35 years old). We decomposed MU spike trains from high-density surface electromyography over the biceps brachii and triceps brachii during isometric ramp contractions to 20% of maximum. Estimates of PICs (i.e. {Delta}F) were computed using the paired MU analysis technique. Regardless of the muscle, peak firing rates of older adults were reduced by ~1.6 pulses per second (pps) (P = 0.0292), and {Delta}F was reduced by ~1.9 pps (P < 0.0001), compared to younger adults. We further found that age predicted {Delta}F in older adults (P = 0.0261), resulting in a reduction of ~1pps per decade, but there was no relationship in younger adults (P = 0.9637). These findings suggest that PICs are reduced in older adults, and, further, age is a significant predictor of estimates of PICs in older adults. Reduced PIC magnitude represents one plausible mechanism for reduced firing rates and weakness in older individuals. KEY POINTSO_LIPersistent inward currents play an important role in the neural control of human movement and are influenced by neuromodulation via monoamines originating in the brainstem. C_LIO_LIDuring aging, motor unit firing rates are reduced, and there is deterioration of brainstem nuclei, which may reduce persistent inward currents in alpha motoneurons. C_LIO_LIHere we show that estimates of persistent inward currents ({Delta}F) of both elbow flexor and extensor motor units are reduced in older adults. C_LIO_LIEstimates of persistent inward currents have a negative relationship with age in the older adults, but not young. C_LIO_LIThis novel mechanism may play a role in alteration motor firing rates that occurs with aging, which may have consequences for motor control. C_LI

physiology↗

bioRxiv2020

The p-coumaroyl arabinoxylan transferase HvAT10 underlies natural variation in whole-grain cell wall phenolic acids in cultivated barley

Phenolic acids in cereal grains have important health-promoting properties and influence digestibility for industrial or agricultural uses. Here we identify alleles of a single BAHD p-coumaroyl arabinoxylan transferase gene, HvAT10, as responsible for the natural variation in cell wall-esterified p-coumaric and ferulic acid in whole grain of a collection of cultivated two-row spring barley genotypes. We show that HvAT10 is rendered non-functional by a premature stop codon mutation in approximately half of the genotypes in our mapping panel. The causal mutation is virtually absent in wild and landrace germplasm suggesting an important function for grain arabinoxylan p-coumaroylation pre-domestication that is dispensable in modern agriculture. Intriguingly, we detected detrimental impacts of the mutated locus on barley grain quality traits. We propose that HvAT10 could be a focus for future grain quality improvement or for manipulating phenolic acid content of wholegrain food products.

plant biology↗

bioRxiv2019

Sensitivity of the paired motor unit analysis for estimation of motoneuron excitability to commonly used constraints and filters

The nervous system has a tremendous ability to modify motoneuron excitability according to task demands through neuromodulatory synaptic input to motoneurons. Neuromodulatory inputs adjust the response of the motoneuron to excitatory and inhibitory ionotropic input and can facilitate the induction of persistent inward currents (PICs). PICs amplify and prolong the motoneuron response to synaptic inputs, and PIC impairment may play a major role in motor deficits observed in pathological conditions. Noninvasive estimation of the magnitude of neuromodulatory input and persistent inward currents in human motoneurons is achieved through a paired motor unit analysis ({Delta}F) that quantifies hysteresis in the firing rates at motor unit recruitment and derecruitment. While the {Delta}F technique is commonly used for estimating motoneuron excitability, computational parameters used for the technique vary across studies. In the present study, we assessed the sensitivity of the {Delta}F technique to several criteria commonly used in selecting motor unit pairs for analysis, as well as to methods used for smoothing the instantaneous motor unit firing rates. Using HD-sEMG and motor unit decomposition we obtained 5,409 motor unit pairs from the triceps brachii of ten healthy individuals during submaximal triangle contractions. The mean (SD) {Delta}F was 4.9 (1.08) pps, consistent with previous work using intramuscular recordings. There was an exponential plateau relationship between {Delta}F and the recruitment time difference between the motor unit pairs, with the plateau occurring at approximately 1 s. There was an exponential decay relationship between {Delta}F and the derecruitment time difference between the motor unit pairs, with the decay stabilizing at approximately 1.5 s. We found that reducing or removing the minimum threshold for the correlation of the rate-rate slope for the two units did not affect {Delta}F values or variance. Additionally, we found that removing motor unit pairs in which the control unit was saturated had no significant effect on {Delta}F. Smoothing filter selection had no substantial effect on {Delta}F values and {Delta}F variance; however, the length and type of smoothing filter affected the minimum recruitment and derecruitment time differences. Our results facilitate interpretation of findings from studies that implement the {Delta}F approach but use different computational parameters.

neuroscience↗

bioRxiv2019

Vaccination against the digestive enzyme Cathepsin B using a YS1646 Salmonella enterica Typhimurium vector provides almost complete protection against Schistosoma mansoni challenge in a mouse model

Schistosoma mansoni threatens hundreds of millions of people in >50 countries. Schistosomulae migrate through the lung and adult worms reside adjacent to the intestinal mucosa. None of the candidate vaccines in current development is designed to elicit a mucosal response. We have repurposed an attenuated Salmonella enterica Typhimurium strain (YS1646) to produce such a vaccine targeting Cathepsin B (CatB), a digestive enzyme important for parasite survival. Promoter-Type 3 secretory signal pairs were screened for protein expression in vitro and transfected into YS1646 to generate candidate vaccine strains. Two strains were selected for in vivo evaluation (nirB_SspH1 and SspH1_SspH1). Female C57BL/6 mice were immunized twice, 3 weeks apart, using six strategies: i) saline gavage (control), ii) the empty YS1646 vector orally (PO) followed by intramuscular recombinant CatB (20g IM rCatB), iii) two doses of IM rCatB, iv) two PO doses of YS1646-CatB, v) IM rCatB then PO YS1646-CatB and vi) PO YS1646-CatB then IM rCatB. Serum IgG responses to CatB were monitored by ELISA. Three weeks after the second dose, mice were challenged with 150 cercariae and sacrificed 7 weeks later to assess adult worm and egg burden (liver and intestine), granuloma size and egg morphology. CatB-specific IgG antibodies were low/absent in the control and PO only groups but rose substantially in other groups (5898-6766ng/mL). The highest response was in animals that received nirB_SspH1 YS1646 PO then IM rCatB. In this group, reductions in worm and intestine/liver egg burden (vs. control) were 93.1% and 79.5%/90.3% respectively (all P<.0001). Granuloma size was reduced in all vaccinated groups (range 32.86-52.83 x103m2) and most significantly in the nirB_SspH1 + CatB IM group (34.74{+/-}3.35 x103m2vs. 62.22{+/-}6.08 x103m2: vs. control P<.01). Many eggs in the vaccinated animals had abnormal morphology. Targeting CatB using a multi-modality approach can provide almost complete protection against S. mansoni challenge.\n\nAuthor SummarySchistosomiasis is a parasitic disease that affects over 250 million people worldwide and over 800 million are at risk of infection. Of the three main species, Schistosoma mansoni is the most widely distributed and is endemic in the Caribbean, South America, Africa, and the Middle East. It causes a chronic disease with severe negative effects on quality of life. Mass drug administration of praziquantel is the only available course of action due to a current lack of vaccines. However, praziquantel does not protect from reinfection. Therefore, a vaccine would be beneficial as a long-term solution to reduce morbidity and transmission of the disease. Our group has repurposed the attenuated YS1646 strain of Salmonella Typhimurium as an oral vaccine vector for the digestive enzyme Cathepsin B of S. mansoni. Oral vaccination followed by an intramuscular dose of recombinant Cathepsin B lead to significant reductions in parasite burden in mice. These animals had the highest titers in serum IgG and intestinal IgA antibodies. This multimodal vaccination approach also elicited both Th1 and Th2 cytokines as seen by the increases in IFN{gamma} and IL-5. Finally, vaccinated mice had reductions in granuloma size along with a higher proportion of morphologically-abnormal eggs. This work demonstrates that a YS1646-based, multimodality, prime-boost immunization schedule can provide nearly complete protection against S. mansoni in a well-established murine model.

immunology↗