Enzymatic Cleavage of Double-Stranded DNA-Encoded Libraries (DELs) to Single-Stranded DELs with Compounds at the 3' End: Its Application in Photo-Crosslinking Selection.

DNA-encoded library (DEL) technology is a crucial tool in pharmaceutical research, rapidly identifying compounds that bind to a target of interest from an extensive pool of compounds. In this study, we propose a new method for generating single-stranded DELs (ssDELs) with compounds at the 3' end. The introduction of uniquely designed hairpin-shaped headpieces containing deoxyuridine (NC-HP) and the use of a cleavage enzyme facilitate the conversion from double-stranded DELs (dsDELs) to such ssDELs.

High-yield and high-purity amide bond formation using DMTMM PF for DNA-encoded libraries.

In this study, we report on the ability of DMTMM PF to improve the amidation reaction. The on-DNA amidation reaction using DMTMM PF demonstrates higher conversion rates than those using HATU or DMTMM Cl, particularly with challenging sterically hindered amines and carboxylic acids. The developed method enables the expansion of available building blocks and the efficient synthesis of high-purity DNA-encoded libraries.

Motor skills training-induced activation of descending pathways mediating cortical command to hindlimb motoneurons in experimental diabetic rats.

Diabetes disrupts the corticospinal tract (CST) system components that control hindlimb and trunk movement, resulting in weakness of the lower extremities. However, there is no information about a method to improve these disorders. This study aimed to investigate the rehabilitative effects of 2 weeks of aerobic training (AT) and complex motor skills training (ST) on motor disorders in streptozotocin-induced type 1 diabetic rats.

Functional and Structural Changes in the Corticospinal Tract of Streptozotocin-Induced Diabetic Rats.

This study aimed to reveal functional and morphological changes in the corticospinal tract, a pathway shown to be susceptible to diabetes. Type 1 diabetes was induced in 13-week-old male Wistar rats administered streptozotocin. Twenty-three weeks after streptozotocin injection, diabetic animals and age-matched control animals were used to demonstrate the conduction velocity of the corticospinal tract.

High-Fat Diet and Age-Dependent Effects of IgA-Bearing Cell Populations in the Small Intestinal Lamina Propria in Mice.

Several studies highlighted that obesity and diabetes reduce immune function. However, changes in the distribution of immunoglobins (Igs), including immunoglobulin-A (IgA), that have an important function in mucosal immunity in the intestinal tract, are unclear. This study aimed to investigate the impaired immune functions in the context of a diet-induced obese murine model via the assessment of the Igs in the intestinal villi.

Properties of Renshaw-like cells excited by recurrent collaterals of pudendal motoneurons in the cat.

Although anatomical studies have indicated pudendal motoneurons to give off recurrent collaterals, they are not considered to make synapses onto interneurons, such as Renshaw cells, and rather terminate their own signals. No study till date has examined interneurons being driven by recurrent collaterals of pudendal motoneurons. Here, we aimed to investigate the existence of Renshaw cells driven by pudendal motoneurons along with the recurrent inhibition of the latter.

Firing properties of medullary expiratory neurons during fictive straining in cats.

Expiratory (E) neurons in the caudal nucleus retroambigualis extend descending spinal axons to the lumbar and sacral spinal cord. Discharge rates of single E neurons were recorded to examine differences in activity of E neurons projecting to the lumbar or sacral spinal cord during fictive straining induced by distention of the colon with a balloon. Firing frequencies of E neurons with descending axons in the thoracic and lumbar spinal cord increased during the repetitive rise of rectum pressure, whereas those of E neurons with descending axons in the sacral spinal cord decreased.

Electrophysiological properties of Ia excitation and recurrent inhibition in cat abdominal motoneurons.

Ia excitation and recurrent inhibition are basic neuronal circuits in motor control in hind limb. Renshaw cells receive synaptic inputs from axon collaterals of motoneurons and inhibit motoneurons and Ia inhibitory interneurons. It is important to know properties of Ia excitation and recurrent inhibition of trunk muscle such as abdominal muscles.

Effects of streptozotocin-induced diabetes on leg muscle contractile properties and motor neuron morphology in rats.

Skeletal muscle fiber subtypes are differentially sensitive to diabetes-related pathology; For example, fast-twitch muscles exhibit severe decreases in contraction force while slow-twitch muscles demonstrate prolonged half-relaxation time. However, such alterations have only been examined after a relatively short period following diabetes onset, with no information available regarding muscle damage caused by longer disease periods (>20 weeks). This study examined alterations in the contractile properties of the medial gastrocnemius (fast-twitch) and soleus (slow-twitch) muscles, as well as morphological changes in their motor neurons 12 and 22 weeks after diabetes onset.

Effect of streptozotocin-induced diabetes on motor representations in the motor cortex and corticospinal tract in rats.

Motor disorders in patients with diabetes are associated with diabetic peripheral neuropathy, which can lead to symptoms such as lower extremity weakness. However, it is unclear whether central motor system disorders can disrupt motor function in patients with diabetes. In a streptozotocin-induced rat model of type 1 diabetes, we used intracortical microstimulation to evaluate motor representations in the motor cortex, recorded antidromic motor cortex responses to spinal cord stimulation to evaluate the function of corticospinal tract (CST) axons, and used retrograde labeling to evaluate morphological alterations of CST neurons.

Effect of streptozotocin-induced diabetes on motoneurons and muscle spindles in rats.

This study examined the alterations in the number and size of motoneurons innervating the medial gastrocnemius (MG) and biceps femoris (BF) motor nuclei in diabetic rats (12 or 22 weeks after injection of streptozotocin) and age-matched controls using retrograde labeling technique. Additionally, morphological alterations of muscle spindles in BF and MG muscles were tested. Significantly fewer labeled MG motoneurons were found in 12- and 22-week diabetic rats as compared with age-matched control animals.

Discharge patterns of abdominal and pudendal nerves during induced defecation in anesthetized cats.

Defecation is thought to be achieved not only by contraction of the colon, but also by a rise in intra-abdominal pressure. In this study we recorded the discharges of nerves innervating the abdominal (Abd) muscles, diaphragm, external anal sphincter (EAS) muscle and pelvic floor (PF) muscles during induced defecation evoked by distention of an expellable balloon to reveal defecation-related muscle activities. The discharges of the Abd muscle and phrenic (Phr) nerves increased when rectal pressure increased.

The size of motoneurons of the gastrocnemius muscle in rats with diabetes.

Alterations in the number and size of motoneurons were studied in the medial gastrocnemius (MG) motor nucleus of diabetic rats (12 or 22 weeks after injection of storeptozotocin) and age-matched controls. Each group contained 6 animals. MG motoneurons were retrogradely labeled by dextran-fluorescein and the number and size of cell bodies were examined.

Synthesis of a stable 1,2-bis(ferrocenyl)diphosphene.

The synthesis and characterization of a stable 1,2-bis(ferrocenyl)diphosphene, wherein a P=P π-bond connects two ferrocenyl units will be reported. This represents an unprecedented example for a d-π electron system containing a heavier pnictogen π-spacer group. Stabilization of the highly reactive P=P π-bond was achieved by steric protection using two bulky ferrocenyl moieties.

The diaphragmatic activities during trunk movements.

In order to investigate how the diaphragm and trunk muscles are recruited during various voluntary movements, we recorded EMG signals and video images simultaneously and analyzed EMGs of the diaphragm and trunk muscles during the voluntary movements that required trunk muscles. During trunk movements, the duration of the diaphragmatic activity became irregular and the intensity of the activity increased. Further analysis revealed that the diaphragmatic activities were consisted of two components, such as respiratory and non-respiratory activities during voluntary movements.

Activity patterns of the diaphragm during voluntary movements in awake cats.

The diaphragm is an important inspiratory muscle, and is also known to participate in the postural function. However, the activity of the diaphragm during voluntary movements has not been fully investigated in awake animals. In order to investigate the diaphragmatic activity during voluntary movements such as extending or rotating their body, we analyzed the electromyogram (EMG) of the diaphragm and trunk muscles in the cat using a technique for simultaneous recordings of EMG signals and video images.

Zwitterionic salts as mild organocatalysts for transesterification.

The exothermic reaction of 3,5-bis(trifluoromethyl)phenyl or 4-nitrophenyl isothiocyanate with 4-pyrrolidinopyridine (PPY) gave the corresponding arylaminothiocarbonylpyridinium salts in quantitative yields. These novel zwitterionic salts were effective as organocatalysts for the transesterification reaction of an equimolar mixture of methyl carboxylates and alcohols in hydrocarbons such as heptane and octane under azeotropic reflux conditions with the removal of methanol. In sharp contrast, PPY was inert as a catalyst under the same reaction conditions.

Morphological study of external oblique motor nerves and nuclei in cats.

In order to clarify the morphological features of peripheral motor nerves and motoneurons that innervate trunk muscles, the size distribution of external oblique (EO) peripheral motor fibers and motoneurons of the thoracic and the lumbar segments were examined. Histograms of the size distribution of EO motor fibers in peripheral nerves after ganglionectomy clearly had a bimodal distribution of small fiber groups and large fiber groups. It is very likely that small fiber groups correspond to gamma motor fibers and large fiber groups to alpha motor fibers.

Vertical eye movement-related type II neurons with downward on-directions in the vestibular nucleus in alert cats.

The vestibular nuclei and the interstitial nucleus of Cajal (INC) have been regarded as key elements of the velocity-to-position integrator for vertical eye movements. This paper reports a class of type II vestibular neurons that receives input from the INC and carries vertical eye movement signals that appear to represent an intermediate stage of the integration process. Extracellular recordings were made from neurons in and near the vestibular nuclei in alert cats.