Kajian Keprihatinan Ahli Akademik Terhadap Tatacara Berpakaian, Sahsiah dan Rupa Diri Pelajar Universiti Malaysia Pahang

Tamadun adalah perkataan Arab “Maddana” yang bermaksud adab, akhlaq, moral dan mempunyai agama yang baik. Manakala hidup bertamadun bermaksud kehidupan yang penuh dengan adab sopan, moral dan berakhlak. Dalam konteks dunia pendidikan hari ini isu tatacara berpakaian, rupa diri, sahsiah dan akhlak pelajar pernah dibincangkan dan diketengahkan di peringkat institusi pengajian tinggi amnya, namun masih tidak menampakkan hasil positif. Kelihatan seolah-olah tiada keseriusan daripada pelbagai pihak untuk mengendalikan dan menjayakan isu ini sebaik mungkin sehingga ke akar umbinya dan secara tidak langsung untuk berusaha menyelesaikannya. Justeru, satu kajian berfokus telah dijalankan terhadap pelajar di Universiti Malaysia Pahang dari pelbagai fakulti. Kajian ini bertujuan meninjau sejauh mana komitmen pensyarah selaku aset penting yang berintegriti tinggi, bernilai dan berakhlak mulia dalam menjalankan amanah mereka mendidik anak bangsa khususnya dalam membangunkan akhlak dan sahsiah diri terpuji dalam kalangan mahasiswa. Kajian ini dilakukan secara tinjauan melalui aplikasi internet iaitu SurveyMonkey kepada lebih dari 100 orang pelajar. Melalui kajian ini terdapat enam perkara yang diperhatikan dan dikaji secara terperinci. Kajian ini berkisar komitmen pelajar dan pensyarah di kampus antaranya ialah komitmen pelajar terhadap pemakaian kad pelajar universiti (kad matrik), komitmen pensyarah memperuntukkan masa dalam kelas bagi menyatakan kepentingan tatacara berpakaian dan rupa diri di kampus, komitmen mengambil tindakan terhadap pelajar yang gagal mematuhi peraturan tatacara berpakaian dan rupa diri, komitmen mengambil tindakan terhadap pelajar yang lewat atau gagal hadir dalam kelas, dan amanah dalam mengisi ruang di slip kehadiran rakan sekuliah dalam kelas. Hasil kajian mendapati bahawa komitmen di kalangan pelajar dan pensyarah kurang memberangsangkan. Perkara ini harus dipandang serius dan sangat membimbangkan kerana penekanan terhadap isu-isu tersebut sangat penting dalam melahirkan pelajar bertamadun iaitu berpengetahuan luas, berkemahiran tinggi dan bersikap, berakhlak serta bersahsiah terpuji

Tactile defensiveness and impaired adaptation of neuronal activity in the Fmr1 knockout mouse model of autism

Sensory hypersensitivity is a common symptom in autism spectrum disorders (ASDs), including Fragile X Syndrome (FXS), and frequently leads to tactile defensiveness. In mouse models of ASDs, there is mounting evidence of neuronal and circuit hyperexcitability in several brain regions, which could contribute to sensory hypersensitivity. However, it is not yet known whether or how sensory stimulation might trigger abnormal sensory processing at the circuit level or abnormal behavioral responses in ASD mouse models, especially during an early developmental time when experience-dependent plasticity shapes such circuits. Using a novel assay, we discovered exaggerated motor responses to whisker stimulation in young Fmr1 knockout (KO) mice (postnatal days (P) 14-16), a model of FXS. Adult Fmr1 KO mice actively avoided a stimulus that was innocuous to wild-type controls, a sign of tactile defensiveness. Using in vivo two-photon calcium imaging of Layer 2/3 barrel cortex neurons expressing GCaMP6s, we found no differences between wild-type and Fmr1 KO mice in overall whisker-evoked activity, though 45% fewer neurons in young Fmr1 KO mice responded in a time-locked manner. Notably, we identified a pronounced deficit in neuronal adaptation to repetitive whisker stimulation in both young and adult Fmr1 KO mice. Thus, impaired adaptation in cortical sensory circuits is a potential cause of tactile defensiveness in autism

A Versatile Method for Viral Transfection of Calcium Indicators in the Neonatal Mouse Brain

The first three postnatal weeks in rodents are a time when sensory experience drives the maturation of brain circuits, an important process that is not yet well understood. Alterations in this critical period of experience-dependent circuit assembly and plasticity contribute to several neurodevelopmental disorders, such as autism, epilepsy, and schizophrenia. Therefore, techniques for recording network activity and tracing neuronal connectivity over this time period are necessary for delineating circuit refinement in typical development and how it deviates in disease. Calcium imaging with GCaMP6 and other genetically encoded indicators is rapidly becoming the preferred method for recording network activity at the single-synapse and single-cell level in vivo, especially in genetically identified neuronal populations. We describe a protocol for intracortical injection of recombinant adeno-associated viruses in P1 neonatal mice and demonstrate its use for longitudinal imaging of GCaMP6s in the same neurons over several weeks to characterize the developmental desynchronization of cortical network activity. Our approach is ideally suited for chronic in vivo two-photon calcium imaging of neuronal activity from synapses to entire networks during the early postnatal period

EZcalcium: Open-Source Toolbox for Analysis of Calcium Imaging Data

Fluorescence calcium imaging using a range of microscopy approaches, such as two-photon excitation or head-mounted “miniscopes,” is one of the preferred methods to record neuronal activity and glial signals in various experimental settings, including acute brain slices, brain organoids, and behaving animals. Because changes in the fluorescence intensity of genetically encoded or chemical calcium indicators correlate with action potential firing in neurons, data analysis is based on inferring such spiking from changes in pixel intensity values across time within different regions of interest. However, the algorithms necessary to extract biologically relevant information from these fluorescent signals are complex and require significant expertise in programming to develop robust analysis pipelines. For decades, the only way to perform these analyses was for individual laboratories to write their custom code. These routines were typically not well annotated and lacked intuitive graphical user interfaces (GUIs), which made it difficult for scientists in other laboratories to adopt them. Although the panorama is changing with recent tools like CaImAn, Suite2P, and others, there is still a barrier for many laboratories to adopt these packages, especially for potential users without sophisticated programming skills. As two-photon microscopes are becoming increasingly affordable, the bottleneck is no longer the hardware, but the software used to analyze the calcium data optimally and consistently across different groups. We addressed this unmet need by incorporating recent software solutions, namely NoRMCorre and CaImAn, for motion correction, segmentation, signal extraction, and deconvolution of calcium imaging data into an open-source, easy to use, GUI-based, intuitive and automated data analysis software package, which we named EZcalcium

Clinicopathological evaluation of chronic traumatic encephalopathy in players of American football

IMPORTANCE: Players of American football may be at increased risk of long-term neurological conditions, particularly chronic traumatic encephalopathy (CTE). OBJECTIVE: To determine the neuropathological and clinical features of deceased football players with CTE. DESIGN, SETTING, AND PARTICIPANTS: Case series of 202 football players whose brains were donated for research. Neuropathological evaluations and retrospective telephone clinical assessments (including head trauma history) with informants were performed blinded. Online questionnaires ascertained athletic and military history. EXPOSURES: Participation in American football at any level of play. MAIN OUTCOMES AND MEASURES: Neuropathological diagnoses of neurodegenerative diseases, including CTE, based on defined diagnostic criteria; CTE neuropathological severity (stages I to IV or dichotomized into mild [stages I and II] and severe [stages III and IV]); informant-reported athletic history and, for players who died in 2014 or later, clinical presentation, including behavior, mood, and cognitive symptoms and dementia. RESULTS: Among 202 deceased former football players (median age at death, 66 years [interquartile range, 47-76 years]), CTE was neuropathologically diagnosed in 177 players (87%; median age at death, 67 years [interquartile range, 52-77 years]; mean years of football participation, 15.1 [SD, 5.2]), including 0 of 2 pre–high school, 3 of 14 high school (21%), 48 of 53 college (91%), 9 of 14 semiprofessional (64%), 7 of 8 Canadian Football League (88%), and 110 of 111 National Football League (99%) players. Neuropathological severity of CTE was distributed across the highest level of play, with all 3 former high school players having mild pathology and the majority of former college (27 [56%]), semiprofessional (5 [56%]), and professional (101 [86%]) players having severe pathology. Among 27 participants with mild CTE pathology, 26 (96%) had behavioral or mood symptoms or both, 23 (85%) had cognitive symptoms, and 9 (33%) had signs of dementia. Among 84 participants with severe CTE pathology, 75 (89%) had behavioral or mood symptoms or both, 80 (95%) had cognitive symptoms, and 71 (85%) had signs of dementia. CONCLUSIONS AND RELEVANCE: In a convenience sample of deceased football players who donated their brains for research, a high proportion had neuropathological evidence of CTE, suggesting that CTE may be related to prior participation in football.This study received support from NINDS (grants U01 NS086659, R01 NS078337, R56 NS078337, U01 NS093334, and F32 NS096803), the National Institute on Aging (grants K23 AG046377, P30AG13846 and supplement 0572063345-5, R01 AG1649), the US Department of Defense (grant W81XWH-13-2-0064), the US Department of Veterans Affairs (I01 CX001038), the Veterans Affairs Biorepository (CSP 501), the Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (grant B6796-C), the Department of Defense Peer Reviewed Alzheimer’s Research Program (grant 13267017), the National Operating Committee on Standards for Athletic Equipment, the Alzheimer’s Association (grants NIRG-15-362697 and NIRG-305779), the Concussion Legacy Foundation, the Andlinger Family Foundation, the WWE, and the NFL

Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible.

To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we adopted a symptom-to-circuit approach in the Fmr1-knockout (Fmr1-/-) mouse model of Fragile X syndrome. Using a go/no-go task and in vivo two-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons and with a decrease in the activity of parvalbumin interneurons in primary visual cortex. Restoring visually evoked activity in parvalbumin cells in Fmr1-/- mice with a chemogenetic strategy using designer receptors exclusively activated by designer drugs was sufficient to rescue their behavioral performance. Strikingly, human subjects with Fragile X syndrome exhibit impairments in visual discrimination similar to those in Fmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in Fragile X syndrome

The A2V mutation as a new tool for hindering Aβ aggregation: A neutron and x-ray diffraction study

We have described a novel C-to-T mutation in the APP gene that corresponds to an alanine to valine substitution at position 673 in APP (A673V), or position 2 of the amyloid-\uce\ub2 (A\uce\ub2) sequence. This mutation is associated with the early onset of AD-type dementia in homozygous individuals, whereas it has a protective effect in the heterozygous state. Correspondingly, we observed differences in the aggregation properties of the wild-type and mutated A\uce\ub2 peptides and their mixture. We have carried out neutron diffraction (ND) and x-ray diffraction (XRD) experiments on magnetically-oriented fibers of A\uce\ub21-28WT and its variant A\uce\ub21-28A2V. The orientation propensity was higher for A\uce\ub21-28A2V suggesting that it promotes the formation of fibrillar assemblies. The diffraction patterns by A\uce\ub21-28WT and A\uce\ub21-28A2V assemblies differed in shape and position of the equatorial reflections, suggesting that the two peptides adopt distinct lateral packing of the diffracting units. The diffraction patterns from a mixture of the two peptides differed from those of the single components, indicating the presence of structural interference during assembly and orientation. The lowest orientation propensity was observed for a mixture of A\uce\ub21-28WT and a short N-terminal fragment, A\uce\ub21-6A2V, which supports a role of A\uce\ub2's N-terminal domain in amyloid fibril formation

TDP-43 Proteinopathy and Motor Neuron Disease in Chronic Traumatic Encephalopathy

Epidemiological evidence suggests that the incidence of amyotrophic lateral sclerosis is increased in association with head injury. Repetitive head injury is also associated with the development of chronic traumatic encephalopathy (CTE), a tauopathy characterized by neurofibrillary tangles throughout the brain in the relative absence of β-amyloid deposits. We examined 12 cases of CTE and, in 10, found a widespread TAR DNA-binding protein of approximately 43 kd (TDP-43) proteinopathy affecting the frontal and temporal cortices, medial temporal lobe, basal ganglia, diencephalon, and brainstem. Three athletes with CTE also developed a progressive motor neuron disease with profound weakness, atrophy, spasticity, and fasciculations several years before death. In these 3 cases, there were abundant TDP-43–positive inclusions and neurites in the spinal cord in addition to tau neurofibrillary changes, motor neuron loss, and corticospinal tract degeneration. The TDP-43 proteinopathy associated with CTE is similar to that found in frontotemporal lobar degeneration with TDP-43 inclusions, in that widespread regions of the brain are affected. Akin to frontotemporal lobar degeneration with TDP-43 inclusions, in some individuals with CTE, the TDP-43 proteinopathy extends to involve the spinal cord and is associated with motor neuron disease. This is the first pathological evidence that repetitive head trauma experienced in collision sports might be associated with the development of a motor neuron disease