Miracle-dz/UniFAR-FTUs huggingface dataset:
Deletion of the microglial transmembrane immune signaling adaptor TYROBP ameliorates Huntington’s disease mouse phenotype

BACKGROUND Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by an expansion of the CAG trinucleotide repeat in the huntingtin gene. Immune activation is abundant in the striatum of HD patients. Detection of active microglia at presymptomatic stages suggests that microgliosis is a key early driver of neuronal dysfunction and degeneration. Recent studies showed that deletion of Tyrobp, a microglial-enriched protein, ameliorates neuronal function in Alzheimer’s disease amyloid and tauopathy mouse models while decreasing components of the complement subnetwork, thus raising the possibility that Tyrobp deletion can be beneficial for HD. METHODS To test the hypothesis that Tyrobp deficiency would be beneficial in a HD model, we placed the Q175 HD mouse model on a Tyrobp-null background. We characterized these mice with a combination of behavioral testing, immunohistochemistry, transcriptomic and proteomic profiling. Further, we evaluated the Q175 microglia-specific gene signature, with and without Tyrobp, by purifying microglia from these mice for transcriptomics. RESULTS Comprehensive analysis of publicly available transcriptomic HD human data revealed that TYROBP network is overactivated in HD putamen. The Q175 mice showed morphologic microglial activation, reduced levels of post-synaptic density-95 protein and motor deficits at 6 and 9 months of age, all of which were ameliorated on the Tyrobp-null background. Gene expression analysis revealed that lack of Tyrobp in the Q175 model does not prevent the decrease in the expression of striatal neuronal genes but reduces pro-inflammatory pathways that are specifically active in HD human brain. Integration of transcriptomic and proteomic data identified that astrogliosis and complement system pathway were reduced after Tyrobp deletion. Results were further validated by immunofluorescence analysis. Microglia-specific HD gene dysregulation, characterized by overexpression of neuronal genes, was also not corrected by Tyrobp deletion. CONCLUSIONS Our data provide molecular and functional support demonstrating that Tyrobp deletion prevents many of the abnormalities in the Q175 HD mouse model, in the absence of correction of striatal neuronal gene expression, suggesting that the Tyrobp pathway is a potential therapeutic candidate for Huntington’s disease.
Effective Infection with Dengue Virus in Experimental Neonate and Adult Mice through the Intranasal Route

As a member of the family Flaviviridae, the dengue virus is transmitted to humans through mosquito vectors. The virus causes dengue fever with flu-like symptoms, life-threatening dengue hemorrhagic fever, and dengue shock syndrome that affects four billion people in 128 countries. It can also be transmitted through atypical routes, such as needle stick injury, vertical transmission, and the receipt of contaminated blood or organs. Although sporadic cases cannot be classified as atypical transmission routes and raise respiratory exposure concerns, the risks remain unclear. Here, we analyzed the respiratory infectivity of the dengue virus in BALB/c suckling and A6 adult mice using the dengue virus serotype 2 and intranasal inoculation. The results showed that the clinical symptoms of intranasally infected mice included excitement, emaciation, malaise, and death, and histopathological changes and viremia dynamics were observed in multiple tissues, including the brain, liver, and spleen. Notably, the DENV serotype 2 showed clear brain tropism after intranasal infection, and viral loads peaked at seven days post-inoculation. Furthermore, the virus was isolated from mouse brains, and the sequence homology between the viral stock and dengue virus isolates was 99.99%. Similar results were observed in adult IFN-α/β receptor-deficient mice. Taken together, our results suggest that the DENV serotype 2 can infect suckling mice and adult immune-deficient mice via the nasal route. The results of our study broaden our perception of atypical dengue transmission routes and may help explain dengue virus infections that occur without the presence of mosquito vectors. Importance Dengue is transmitted mainly via mosquito vectors. Flu-like dengue fever or life-threatening severe dengue threatens four billion people in 128 countries. Non-vector dengue cases have occurred occasionally since 1990. These cases cannot be classified as atypical transmission routes and are suspected to have arisen via sexual or respiratory transmission. Recently, the sexual transmission of dengue has been confirmed in humans. The respiratory infectivity of other members of the Flaviviridae family, such as Zika and Japanese encephalitis viruses, has been determined under experimental conditions. The potential for respiratory infection with the dengue virus has not yet been confirmed. In this study, we analyzed the respiratory infectivity of the dengue virus in suckling mice and adult immunodeficient mice via intranasal inoculation, thereby exploring the potential for respiratory transmission in cases with non-vector dengue infection, especially for patients who were exposed to dengue virus contaminants.
Single-cell analysis of gene expression in the substantia nigra pars compacta of a pesticide-induced mouse model of Parkinson’s disease

Abstract Exposure to pesticides in humans increases the risk of Parkinson’s disease (PD), but the mechanisms remain poorly understood. To elucidate these pathways, we dosed C57BL/6J mice with a combination of the pesticides maneb and paraquat. Behavioral analysis revealed motor deficits consistent with PD. Single-cell RNA sequencing of substantia nigra pars compacta revealed both cell-type-specific genes and genes expressed differentially between pesticide and control, including Fam241b, Emx2os, Bivm, Gm1439, Prdm15, and Rai2. Neurons had the largest number of significant differentially expressed genes, but comparable numbers were found in astrocytes and less so in oligodendrocytes. In addition, network analysis revealed enrichment in functions related to the extracellular matrix. These findings emphasize the importance of support cells in pesticide-induced PD and refocus our attention away from neurons as the sole agent of this disorder.
Canine Elbow Dysplasia

The key features of Canine elbow dysplasia, a developmental orthopaedic condition that commonly affects young 4-8 month old dogs from large breeds like German Shepherds, Bernese Mountains, Labradors, Rottweilers and Golden Retrievers are discussed. The diagnosis, treatment methodologies and management regime for the same are highlighted.
Optogenetic Application to Investigating Cell Behavior and Neurological Disease

Cells reside in a dynamic microenvironment that presents them with regulatory signals that vary in time, space, and amplitude. The cell, in turn, interprets these signals and accordingly initiates downstream processes including cell proliferation, differentiation, migration, and self-organization. Conventional approaches to perturb and investigate signaling pathways (e.g., agonist/antagonist addition, overexpression, silencing, knockouts) are often binary perturbations that do not offer precise control over signaling levels, and/or provide limited spatial or temporal control. In contrast, optogenetics leverages light-sensitive proteins to control cellular signaling dynamics and target gene expression and, by virtue of precise hardware control over illumination, offers the capacity to interrogate how spatiotemporally varying signals modulate gene regulatory networks and cellular behaviors. Recent studies have employed various optogenetic systems in stem cell, embryonic, and somatic cell patterning studies, which have addressed fundamental questions of how cell-cell communication, subcellular protein localization, and signal integration affect cell fate. Other efforts have explored how alteration of signaling dynamics may contribute to neurological diseases and have in the process created physiologically relevant models that could inform new therapeutic strategies. In this review, we focus on emerging applications within the expanding field of optogenetics to study gene regulation, cell signaling, neurodevelopment, and neurological disorders, and we comment on current limitations and future directions for the growth of the field.
CINCINNATA-Like TCP Transcription Factors in Cell Growth – An Expanding Portfolio

Post-mitotic cell growth is a key process in plant growth and development. Cell expansion drives major growth during morphogenesis and is influenced by both endogenous factors and environmental stimuli. Though both isotropic and anisotropic cell growth can contribute to organ size and shape at different degrees, anisotropic cell growth is more likely to contribute to shape change. While much is known about the mechanisms that increase cellular turgor and cell-wall biomass during expansion, the genetic factors that regulate these processes are less studied. In the past quarter of a century, the role of the CINCINNATA-like TCP (CIN-TCP) transcription factors has been well documented in regulating diverse aspects of plant growth and development including flower asymmetry, plant architecture, leaf morphogenesis, and plant maturation. The molecular activity of the CIN-TCP proteins common to these biological processes has been identified as their ability to suppress cell proliferation. However, reports on their role regulating post-mitotic cell growth have been scanty, partly because of functional redundancy among them. In addition, it is difficult to tease out the effect of gene activity on cell division and expansion since these two processes are linked by compensation, a phenomenon where perturbation in proliferation is compensated by an opposite effect on cell growth to keep the final organ size relatively unaltered. Despite these technical limitations, recent genetic and growth kinematic studies have shown a distinct role of CIN-TCPs in promoting cellular growth in cotyledons and hypocotyls, the embryonic organs that grow solely by cell expansion. In this review, we highlight these recent advances in our understanding of how CIN-TCPs promote cell growth.
Case Report: Tricuspid Annuloplasty for Right-Sided Congestive Heart Failure Secondary to Pulmonary Hypertension in a Dog

An 11-year-old, 12.3-kg, female Miniature Dachshund was presented to our institution with ascites of unknown etiology. The dog had been administered moxidectin for 3 years to treat a heartworm infection. Thoracic radiographs showed enlargement of the right heart. Echocardiography revealed right atrial and ventricular dilatation as well as flattening of the interventricular septum. Heartworm was identified in the main pulmonary artery, which was dilated. Tricuspid regurgitation (TR) was observed using color Doppler ultrasonography, and 2.5 L of ascites were removed. The dog was diagnosed with pulmonary hypertension, severe TR, and right-sided congestive heart failure. Except at the initial site, heartworm was not detected using echocardiography, and the antigen test was negative. However, pharmacological treatment did not improve the right-sided congestive heart failure. Instead, De Vega tricuspid annuloplasty (TAP) was performed on the beating heart under cardiopulmonary bypass with the owner's consent. Sutures terminated between the two commissures in the middle of the annulus and were secured using another pledget. Annular reduction was performed by tying down the plication suture while the cylindrical sizer was inserted into the tricuspid valve orifice. The size of the cylindrical sizer was 16 mm, which was set based on the height and width of the septal leaflet. A 6-month follow-up showed a reduction of TR and right-sided volume overload with no evidence of ascites retention/recurrence or any other complication. Our findings indicate that TAP may be a valid treatment option for dogs with right-sided congestive heart failure caused by secondary TR.
Major Impact of Coping Styles on Anxiety and Depression Symptoms in Healthcare Workers During the Outbreak of COVID-19

Background In the early days of COVID-19 outbreak, the normally orderly health system was severely challenged by large numbers of feverish patients and shortage of healthcare workers. The outbreak played a harmful role in the mental health of these healthcare workers. Objective We aim to assess the prevalence of moderate or severe anxiety and depression symptoms (ADSs) of healthcare workers in different regions during COVID-19 disaster and identify the potential risk factors. Methods We did a cross-sectional study on ADS of healthcare workers in epicenter-Hubei province and regions in lower epidemic-other provinces by questionnaire online. The data of ADS, the demographic characteristics, occupational exposure, physical condition, family situation, and coping styles were collected and analyzed. Results A total of 24.68% of the respondents had experienced moderate or severe ADS. Moderate or severe ADSs were in a higher prevalence in Hubei (32.39%) than other provinces (18.22%). Suspicious symptoms on their own and in family members were independent risk factors of moderate or severe ADS of all health workers. Working on the frontline was the independent risk factor for participants in Hubei province, whereas quarantine was the independent risk factor for those in other provinces. Moreover, among all participants, those with negative coping style were more than four times more likely to have moderate or severe ADS than those with positive coping style. Conclusion Moderate or severe ADSs were in a higher prevalence in healthcare workers of Hubei province during COVID-19 outbreak. The coping style may have major impact on ADS in such situation.
Symmetrical Dimethylarginine as a Diagnostic Parameter in Hermann's Tortoises (Testudo hermanni)

Background Despite improvements in habitational conditions, kidney disease is relatively common in tortoises. Objectives Purpose of this study was the establishment of Symmetrical dimethylarginine (SDMA) reference values for clinically healthy Hermann's Tortoises. Animals Clinically healthy Hermann's Tortoises (n = 131) were included in the period from October 2017 to September 2019. Methods Creatinine and other biomarkers were tested at IDEXX Laboratories, Germany using residual blood samples from Hermann's tortoises. SDMA was measured with the IDEXX test and verified by liquid chromatography-mass spectrometry at IDEXX Laboratories, USA. Results SDMA values ranged from 1 to 21 μg/dl (n = 131) for the IDEXX SDMA Test and SDMA values ranged from 1 to 17 μg/dl (n = 82) for LC-MS. For the comparison of the two measuring systems, the following results were obtained R2 = 0.75 (p < 0.001). Conclusion and Clinical Importance SDMA can be measured in Hermann's Tortoises and the reference values range in clinically healthy animals is comparable to that of dogs and cats.
Lactobacillus crispatus Strain KT-11 S-Layer Protein Inhibits Rotavirus Infection

S-layer proteins (SLPs), which are present in the external layer of certain strains of lactic acid bacteria isolated from the intestinal tract, are known to recognize and bind to specific proteins and glycan structures and contribute to adsorption to the host intestinal mucosa. The binding properties of certain SLPs are considered to exert a competitive inhibitory effect on infection because similar properties are involved in the infection mechanisms of several viruses. However, little is known regarding whether SLPs directly inhibit viral infection. In the present study, we investigated the effect of an SLP of the Lactobacillus crispatus KT-11 strain, a probiotic strain isolated from a healthy human infant, on human rotavirus infection. The impact of KT-11 lithium chloride extract (KT-11 LE), which contains SLP, on the infection of the P[4] genotype human rotavirus strain DS-1 was evaluated by monitoring the amplification of viral protein 6 (VP6) expression in human intestinal epithelial Caco-2 cells by quantitative reverse transcription-polymerase chain reaction assay after infection. KT-11 LE showed a significant suppressive effect on DS-1 infection in a dose-dependent manner with pre-infection treatment, whereas post-infection treatment was not effective. A 45 KDa protein isolated from KT-11 LE was investigated for homology using the BLAST database and was found to be a novel SLP. KT-11 SLP concentrate (KT-11 SLP) significantly inhibited the proliferative process of the DS-1 strain but not that of the P[8] genotype human rotavirus strain Wa. KT-11 SLP exerted significant inhibitory effect on DS-1 infection by pre-infection treatment even after digestion with gastric juice up to 2 h. Our results provided crucial evidence that SLPs from certain Lactobacillus strains can inhibit human rotavirus infection of intestinal epithelial cells.
Patients With Autoimmune Thyroiditis Present Similar Immunological Response to COVID-19 BNT162b2 mRNA Vaccine With Healthy Subjects, While Vaccination May Affect Thyroid Function: A Clinical Study

Background This is the first study, that aimed: a) to compare immune response, namely the kinetics of neutralizing antibodies (Nabs), after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) between patients with autoimmune thyroiditis and controls, and b) to investigate changes in thyroid function in healthy subjects with no history of thyroid dysfunction before and after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech). Methods The entire study consisted of two sub-studies. In the first sub-study, NAbs levels after BNT162b2 mRNA vaccination were compared between 56 patients with autoimmune thyroiditis and 56 age and gender-matched healthy controls from the day of the first dose until a period of up to three months after the second dose. In the second sub-study, thyroid hormones (T3, T4, TSH) and thyroid auto-antibodies levels (anti-TG, anti-TPO) of 72 healthy subjects with no history of thyroid disease were examined before (D1) and one month after completion of the second dose (D50). Results Among patients with autoimmune thyroiditis, the median neutralizing inhibition on D22, immediately before second dose, was 62.5%. One month later (D50), values increased to 96.7%, while three months after the second dose NAbs titers remained almost the same (94.5%). In the healthy group, median NAbs levels at D22 were 53.6%. On D50 the median inhibition values increased to 95.1%, while after three months they were 89.2%. The statistical analysis did not show significant differences between two groups (p-values 0.164, 0.390, 0.105 for D22, D50 and three months). Regarding changes in thyroid function, the mean value for T4 before vaccination was 89.797 nmol/L and one month after the second dose was 89.11 nmol/L (p-value=0.649). On D1 the mean T3 value was 1.464 nmol/L, which dropped to 1.389 nmol/L on D50 (p-value = 0.004). For TSH, mean levels were 2.064 mIU/ml on D1 and fell to 1.840 mIU/ml one month after the second dose (p-value=0.037). Despite decrease, all thyroid hormone levels remained within the normal range. No changes were found for anti-TPO or anti-TG. Conclusions This study provided evidence that patients with autoimmune thyroiditis present similar immunological response to COVID-19 BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) with healthy subjects, while vaccination may affect thyroid function.
Hope for “Continued Vitality”: Qualitative Study of Adults With Traumatic Brain Injury and Low Mood on Their Rehabilitation

Objective Depression is highly comorbid with traumatic brain injury (TBI) with often complex and interacting symptomology that contributes to the experience of disability. Comorbid depression results in poorer TBI rehabilitation and downstream participation outcomes yet perspectives of this group regarding person-centered care is unknown. Purpose This study aimed to explicate the perspectives of persons with TBI and depression on their values, preferences, and desired outcomes for optimal rehabilitation. Methods A qualitative descriptive approach was taken. Thirteen adults [mean age: 40.5 (standard deviation 9.8)] diagnosed with TBI and with self-reported low mood were recruited through convenience sampling. Participants were predominantly female (n = 12) with concussion/mild TBI and at least 6 months post-injury. One-on-one, semi-structured interviews were conducted by phone with Canadian participants (March-May 2020). Interviews were transcribed; data were analyzed thematically by two researchers and the thematic map refined by the research team. Results Three themes were identified on values, preferences, and desired outcomes in person-centered care. Participants valued “validation” from healthcare providers and the health system to feel seen and believed about their conditions and concerns. They preferred for healthcare providers to “share the burden of managing care” through improved interactions and better access to concussion care. Participants expressed that “meaningful outcomes” were to be symptom free, to resume valued life activities, and to be able to adapt/be resilient. The latter indicated hope for “continued vitality” for life participation despite past and ongoing challenges. Conclusions Many adults with TBI and self-identified low mood expressed rehabilitation experiences that were invalidating. Their identified values, preferences, and desired outcomes provide directions for better person-centered care by healthcare providers and health systems to support participation.
Charity Begins at Home: Understanding the Role of Corporate Social Responsibility and Human Resource Practices on Employees’ Attitudes During COVID-19 in the Hospitality Sector

The COVID-19 outbreak wreaked havoc on the hospitality business, resulting in significant layoffs, salary cuts, and unpaid leaves globally. This study uses the sensemaking theory to investigate how COVID-19 induced unfavorable human resource (HR) practices affect the link between perceived corporate social responsibility (CSR) and employee identification and commitment. We tested this model using the data collected from 392 hospitality sector employees in Pakistan. The results reveal that “cut in salaries” and “work from home” positively moderate CSR’s impact on employees’ identification and commitment. On the other hand, employee layoff and leave without pay do not impact the positive relationship between CSR and employees’ attitudes. Furthermore, the study finds that CSR during this pandemic has a significant positive impact on employees’ attitudes. However, this relationship becomes insignificant for employees who reported unfavorable HR practices in their organizations. The finding further reveals that CSR’s impact during COVID-19 on employees’ attitudes is moderated by the different levels of CSR importance in employees’ minds. This evidence is significant since HR practices implemented during this crisis need to be identified and framed to understand the effects of CSR on employee commitment and identification. CSR involvement in the pandemic can help managers keep their employees committed to organizations; only if this charity begins from their internal stakeholders first.
Oral Immunotherapy in Food Allergy: A Critical Pediatric Perspective

There is evidence that in children with persistent IgE-mediated food allergy (FA) to cow's milk, hen's egg, and peanut, oral allergen-specific immunotherapy (OIT) may increase the reaction threshold to the culprit food allergen(s). OIT may protect patients from the occurrence of severe reactions in case of accidental ingestion of the culprit food during treatment. Notwithstanding, many gaps are still unsolved, including safety issues, identification of predictive biomarkers, and post-desensitization efficacy. In this perspective, the use of omalizumab (Anti-IgE monoclonal antibody) has been proposed as an adjunctive treatment to OIT in order to reduce the risk of allergic reactions related to OIT. This review aims to summarize the current evidence and unmet needs on OIT in children with FA to enhance the development of longitudinal, prospective, and well-designed studies able to fill the current gaps soon.