Parallel motion vision pathways in the brain of a tropical bee.

Spatial orientation is a prerequisite for most behaviors. In insects, the underlying neural computations take place in the central complex (CX), the brain's navigational center. In this region different streams of sensory information converge to enable context-dependent navigational decisions. Accordingly, a variety of CX input neurons deliver information about different navigation-relevant cues. In bees, direction encoding polarized light signals converge with translational optic flow signals that are suited to encode the flight speed of the animals. The continuous integration of speed and directions in the CX can be used to generate a vector memory of the bee's current position in space in relation to its nest, i.e., perform path integration. This process depends on specific, complex features of the optic flow encoding CX input neurons, but it is unknown how this information is derived from the visual periphery. Here, we thus aimed at gaining insight into how simple motion signals are reshaped upstream of the speed encoding CX input neurons to generate their complex features. Using electrophysiology and anatomical analyses of the halictic bees Megalopta genalis and Megalopta centralis, we identified a wide range of motion-sensitive neurons connecting the optic lobes with the central brain. While most neurons formed pathways with characteristics incompatible with CX speed neurons, we showed that one group of lobula projection neurons possess some physiological and anatomical features required to generate the visual responses of CX optic-flow encoding neurons. However, as these neurons cannot explain all features of CX speed cells, local interneurons of the central brain or alternative input cells from the optic lobe are additionally required to construct inputs with sufficient complexity to deliver speed signals suited for path integration in bees.

The neuroprotective effect of human uncoupling protein 2 (hUCP2) requires cAMP-dependent protein kinase in a toxin model of Parkinson's disease.

Parkinson's disease (PD), caused by selective loss of dopaminergic (DA) neurons in the substantia nigra, is the most common movement disorder with no cure or effective treatment. Exposure to the mitochondrial complex I inhibitor rotenone recapitulates pathological hallmarks of PD in rodents and selective loss of DA neurons in Drosophila. However, mechanisms underlying rotenone toxicity are not completely resolved. We previously reported a neuroprotective effect of human uncoupling protein 2 (hUCP2) against rotenone toxicity in adult fly DA neurons. In the current study, we show that increased mitochondrial fusion is protective from rotenone toxicity whereas increased fission sensitizes the neurons to rotenone-induced cell loss in vivo. In primary DA neurons, rotenone-induced mitochondrial fragmentation and lethality is attenuated as the result of hucp2 expression. To test the idea that the neuroprotective mechanism of hUCP2 involves modulation of mitochondrial dynamics, we detect preserved mitochondrial network, mobility and fusion events in hucp2 expressing DA neurons exposed to rotenone. hucp2 expression also increases intracellular cAMP levels. Thus, we hypothesize that cAMP-dependent protein kinase (PKA) might be an effector that mediates hUCP2-associated neuroprotection against rotenone. Indeed, PKA inhibitors block preserved mitochondrial integrity, movement and cell survival in hucp2 expressing DA neurons exposed to rotenone. Taken together, we present strong evidence identifying a hUCP2-PKA axis that controls mitochondrial dynamics and survival in DA neurons exposed to rotenone implicating a novel therapeutic strategy in modifying the progression of PD pathogenesis.

A Case of Leukemic Pleural Infiltration in the Blast Crisis Phase of Chronic Myeloid Leukemia: An Unusual Extramedullary Involvement.

The development of pleural effusion in chronic myeloid leukemia (CML) is not well-understood and rarely documented in literature. Extramedullary involvement (EMI), which occurs in about 10% of CML cases, typically affects lymph nodes and the spleen. Instances of extensive infiltration of leukemic cells into the pleura are infrequently reported in CML. Here, we report a case of 41-year-old man experiencing significant bilateral pleural effusion with leukemic infiltration during the blast crisis (BC) phase of refractory CML. Examination of the pleural fluid revealed cells with morphological characteristics of myeloblasts. Although very rare, pleural leukemic infiltration should be considered as a cause of pleural effusion in patients with CML, especially in the BC phase.

Analyzing Tumor Budding Scores in Invasive Breast Carcinoma: A Tertiary Care Center Study in South India.

Introduction and Aim: Tumor budding is a distinctive phenomenon which involves the presence of small clusters or individual cancer cells at the invasive front of tumors. Tumor budding has garnered attention due to its potential implications for prognosis, treatment strategies, and our understanding of cancer progression. Our aim is to study the distribution of tumor buds and its scoring in patients with infiltrating breast carcinoma and to associate with other histopathological parameters like the size of the tumor, its grade, lymphovascular invasion, and lymph node metastasis. Materials and Methods: This was a study analyzing the data of 70 resected specimens of primary breast carcinomas and providing a descriptive overview. Tumor budding was recognized, counted, and graded in hematoxylin and eosin slides. The cases were classified as low (0-4), intermediate (5-9), and high (≥10 buds) based on the count of tumor buds. Tumor budding has significant correlation with tumor grade and tumor size. Results: Of the 70 cases, 60 cases (85.71%) were diagnosed as invasive ductal carcinoma NOS. The majority [38 (54.28%)] of the cases showed an intermediate tumor budding score of 5-9/10 HPF. Conclusion: Evaluation of tumor budding allows pathologists and oncologists to gather valuable information about the tumor's biological aggressiveness and potential for metastasis. It also helps in better risk stratification of patients, enabling a more personalized and tailored approach to treatment planning. In conclusion, assessing tumor budding in breast carcinoma holds significant clinical importance in the management and prognosis of this disease.

Exploring the Clinical and Hematological Characteristics of Beta-Thalassemia Trait: A Comprehensive Analysis in a Tertiary Care Hospital Setting.

Beta-thalassemia is one of the most common inherited hematological diseases caused by more than 350 mutations in the ß-globin gene (HBB). Beta-thalassemia carrier or trait is associated with defects in one allele of the HBB gene. The majority of beta-thalassemia trait cases remain concealed in society and remain unnoticed as they are mostly asymptomatic or present with mild symptoms of anemia. There is a 25% chance of having children with beta-thalassemia major and a 50% chance of having carrier babies when two people with beta-thalassemia trait are married. Hence, it is important to identify the individuals with beta-thalassemia trait and provide counseling to understand the risks of pregnancy and its outcome. Aim To study the identification of beta-thalassemia trait cases along with their clinical findings and hematological correlation. Materials and methods Study Design This was a retrospective study conducted at Saveetha Medical College and Hospital for a period of four years from January 2020 to December 2023. Inclusion Criteria Age group more than 18 years, antenatal mother, cases of anemia who were refractory to iron treatment, and screening of family members in the positive cases of beta-thalassemia trait. Exclusion Criteria History of blood transfusion within three months was excluded. Data Collection  A total number of 837 cases were screened to rule out the presence of beta-thalassemia trait/hemoglobin (Hb) variants. A 2 mL of intravenous blood samples were collected in an ethylene diamine tetraacetic acid (EDTA) vacutainer tube and processed in a Sysmex XN 1000 (Hyogo, Japan: Sysmex Corporation) automated hematology analyzer. The hematological parameters were analyzed. Statistical Analysis The study included both descriptive and analytical characteristics. Mean and standard deviation (SD) were calculated for all the hematological parameters. Beta-thalassemia trait was diagnosed with an HbA2 level of more than 4.0% through high-performance liquid chromatography (HPLC) analysis. Results  Among the 837 samples studied for HPLC screening, 74 (8.8%) cases were found to have beta-thalassemia trait. The age group included was from 18 years to 56 years. Of 74 cases studied, 32(43%) were females and 42(57%) were males. Among the 74 cases studied, the Mentzer index <13 was seen in 58 (78%) cases and the Mentzer index >13 was seen in 16 cases (22%). Thirty-four cases (46%) of beta-thalassemia traits presented to the hospital with a history of fever for evaluation and antenatal screening accounted for 19 cases (26%). The mean red blood cell (RBC) count was 5.5 million/cu.mm; mean corpuscular volume (MCV) was 63.8 fL; mean corpuscular hemoglobin (MCH) was 19.6 pg; red cell distribution width coefficient of variation (RDW-CV) was 17.8%. Among the 74 cases studied, 37(46%) cases had an Hb of more than 11 g/dL, 22 cases had mild anemia, 12 cases had moderate anemia, and three cases had severe anemia. Conclusion This study concluded that regular monitoring of the Mentzer index along with HPLC analysis is an effective approach in identifying beta-thalassemia trait cases and further providing genetic counseling among the couples that will help in reducing high-risk pregnancy and the birth of a child with thalassemia major.

Extended lifespan in female Drosophila melanogaster through late-life calorie restriction.

Calorie restriction has many beneficial effects on healthspan and lifespan in a variety of species. However, how late in life application of caloric restriction can extend fly life is not clear. Here we show that late-life calorie restriction increases lifespan in female Drosophila melanogaster aged on a high-calorie diet. This shift results in rapid decrease in mortality rate and extends fly lifespan. In contrast, shifting female flies from a low- to a high-calorie diet leads to a rapid increase in mortality and shorter lifespan. These changes are mediated by immediate metabolic and physiological adaptations. One of such adaptation is rapid adjustment in egg production, with flies directing excess energy towards egg production when shifted to a high diet, or away from reproduction in females shifted to low-caloric diet. However, lifelong female fecundity reveals no associated fitness cost due to CR when flies are shifted to a high-calorie diet. In view of high conservation of the beneficial effects of CR on physiology and lifespan in a wide variety of organisms, including humans, our findings could provide valuable insight into CR applications that could provide health benefits later in life.

A neuroprotective role of the human uncoupling protein 2 (hUCP2) in a Drosophila Parkinson's disease model.

Parkinson's disease (PD), caused by selective loss of dopaminergic (DA) neurons in the substantia nigra pars compacta, is the most common movement disorder. While its etiology remains unknown, mitochondrial dysfunction is recognized as one of the major cellular defects contributing to PD pathogenesis. Mitochondrial uncoupling protein 2 (UCP2) has been implicated in neuroprotection in several neuronal injury models. Here we show that hucp2 expression in Drosophila DA neurons under the control of the tyrosine hydroxylase (TH) promoter protects those flies against the mitochondrial toxin rotenone-induced DA neuron death, head dopamine depletion, impaired locomotor activity and energy deficiency. Under normal conditions, hUCP2 flies maintain an enhanced locomotor activity and have higher steady-state ATP levels suggesting improved energy homeostasis. We show that while no increased mitochondrial DNA content or volume fraction is measured in hUCP2 flies, augmented mitochondrial complex I activity is detected. Those results suggest that it is increased mitochondrial function but not mitochondrial biogenesis that appears responsible for higher ATP levels in hUCP2 flies. Consistent with this notion, an up-regulation of Spargel, the Drosophila peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1) homologue is detected in hUCP2 flies. Furthermore, a Spargel target gene Tfam, the mitochondrial transcription factor A is up-regulated in hUCP2 flies. Taken together, our results demonstrate a neuroprotective effect of hUCP2 in DA neurons in a Drosophila sporadic PD model. Moreover, as the TH promoter activity is present in both DA neurons and epidermis, our results reveal that hucp2 expression in those tissues may act as a stress signal to trigger Spargel activation resulting in enhanced mitochondrial function and increased energy metabolism.

Olfactory Strategies in the Defensive Behaviour of Insects.

Most animals must defend themselves in order to survive. Defensive behaviour includes detecting predators or intruders, avoiding them by staying low-key or escaping or deterring them away by means of aggressive behaviour, i.e., attacking them. Responses vary across insect species, ranging from individual responses to coordinated group attacks in group-living species. Among different modalities of sensory perception, insects predominantly use the sense of smell to detect predators, intruders, and other threats. Furthermore, social insects, such as honeybees and ants, communicate about danger by means of alarm pheromones. In this review, we focus on how olfaction is put to use by insects in defensive behaviour. We review the knowledge of how chemical signals such as the alarm pheromone are processed in the insect brain. We further discuss future studies for understanding defensive behaviour and the role of olfaction.

The Role of Citrate Transporter INDY in Metabolism and Stem Cell Homeostasis.

I'm Not Dead Yet (Indy) is a fly gene that encodes a homologue of mammalian SLC13A5 plasma membrane citrate transporter. Reducing expression of Indy gene in flies, and its homologues in worms, extends longevity. Indy reduction in flies, worms, mice and rats affects metabolism by regulating the levels of cytoplasmic citrate, inducing a state similar to calorie restriction. Changes include lower lipid levels, increased insulin sensitivity, increased mitochondrial biogenesis, and prevention of weight gain, among others. The INDY protein is predominantly expressed in fly metabolic tissues: the midgut, fat body and oenocytes. Changes in fly midgut metabolism associated with reduced Indy gene activity lead to preserved mitochondrial function and reduced production of reactive oxygen species. All these changes lead to preserved intestinal stem cell homeostasis, which has a key role in maintaining intestinal epithelium function and enhancing fly healthspan and lifespan. Indy gene expression levels change in response to caloric content of the diet, inflammation and aging, suggesting that INDY regulates metabolic adaptation to nutrition or energetic requirements by controlling citrate levels.

INDY-From Flies to Worms, Mice, Rats, Non-Human Primates, and Humans.

I'm Not Dead Yet (Indy) is a fly homologue of the mammalian SLC13A5 (mSLC13A5) plasma membrane citrate transporter, a key metabolic regulator and energy sensor involved in health, longevity, and disease. Reduction of Indy gene activity in flies, and its homologs in worms, modulates metabolism and extends longevity. The metabolic changes are similar to what is obtained with caloric restriction (dietary restriction). Similar effects on metabolism have been observed in mice and rats. As a citrate transporter, INDY regulates cytoplasmic citrate levels. Indy flies heterozygous for a P-element insertion have increased spontaneous physical activity, increased fecundity, reduced insulin signaling, increased mitochondrial biogenesis, preserved intestinal stem cell homeostasis, lower lipid levels, and increased stress resistance. Mammalian Indy knockout (mIndy-KO) mice have higher sensitivity to insulin signaling, lower blood pressure and heart rate, preserved memory and are protected from the negative effects of a high-fat diet and some of the negative effects of aging. Reducing mIndy expression in human hepatocarcinoma cells has recently been shown to inhibit cell proliferation. Reduced Indy expression in the fly intestine affects intestinal stem cell proliferation, and has recently been shown to also inhibit germ cell proliferation in males with delayed sperm maturation and decreased spermatocyte numbers. These results highlight a new connection between energy metabolism and cell proliferation. The overrall picture in a variety of species points to a conserved role of INDY for metabolism and health. This is illustrated by an association of high mIndy gene expression with non-alcoholic fatty liver disease in obese humans. mIndy (mSLC13A5) coding region mutations (e.g., loss-of-function) are also associated with adverse effects in humans, such as autosomal recessive early infantile epileptic encephalopathy and Kohlschütter-Tönz syndrome. The recent findings illustrate the importance of mIndy gene for human health and disease. Furthermore, recent work on small-molecule regulators of INDY highlights the promise of INDY-based treatments for ameliorating disease and promoting healthy aging.

Trichilemmal Carcinoma of Scalp Masquerading as Squamous Cell Carcinoma: A Report of a Rare Case with Histogenesis and Literature Review.

Trichilemmal carcinoma is a rare malignant adnexal neoplasm of follicular type usually seen over the sun-exposed areas of elderly people. We present a report of a 60-year-old male with ulceroproliferative lesion over the occipital region of the scalp for 2 months, clinically diagnosed as squamous cell carcinoma. A wide local excision was done, and histopathological examination showed atypical clear cells with abrupt keratinization. The histogenesis and other differential diagnoses are discussed.

Performance of molecular and serologic tests for the diagnosis of scrub typhus.

Diagnosis of scrub typhus, caused by the bacterium Orientia tsutsugamushi, is challenging because of the overlap of its non-specific symptoms with other infections coupled with the lack of sufficient data on the performance of diagnostic tests. Early diagnosis of scrub typhus is crucial to improve outcomes and this study evaluates the diagnostic performance of various tests. The present study aims at assessing the accuracy of various rapid diagnostic tests, serologic tests, and nucleic acid amplification methods on well-characterized patient samples. Adult patients with acute febrile illness and manifestations suggestive of scrub typhus confirmed by positive PCR in the blood, eschar or tissue were characterized as cases. Patients with acute febrile illness and a confirmed alternate etiology such as culture-confirmed typhoid, smear/PCR positive for malaria, PCR/NS1 antigen positive for dengue, PCR positive for influenza, PCR/MAT positive for leptospirosis, PCR positive for spotted fever were characterized as controls with other infections. The healthy controls consisted of subjects from the same geographic region. We performed the following tests on blood samples for scrub typhus and calculated the sensitivity, specificity, positive predictive value, and negative predictive value: (1) Quantitative real time PCR using 47kDa gene (qPCR); (2) Conventional PCR using 56kDa gene (cPCR); (3) Loop-mediated isothermal amplification assay (LAMP assay); (4) Immunofluorescence assay (IFA); (5) Enzyme-linked immunosorbent assay (ELISA); (6) Weil-Felix test(WF test); and (7) Immunochromatographic Rapid Diagnostic Test (RDT).Among the 316 participants, 158 had confirmed scrub typhus (cases) and 158 were controls. ELISA and RDT detecting Orientia tsutsugamushi specific IgM antibodies had excellent discriminative potential with sensitivities and specificities of 92%, 94% and 92%, 92% respectively. The sensitivity and specificity of IFA were found to be 95% and 74% respectively. IgM serology had a false positivity rate of 8% with other acute febrile illnesses such as dengue, leptospirosis and spotted fever due to the nonspecific binding of the pentavalent IgM. LAMP assay had 91.7% sensitivity and 77.2% specificity while qPCR provided excellent sensitivity (97%) and perfect specificity. In conclusion, ELISA and RDT detecting Orientia tsutsugamushi specific IgM antibodies have excellent sensitivity and specificity while the accuracy of IFA is suboptimal for the diagnosis of scrub typhus. Given its perfect specificity and superior sensitivity, qPCR is preferred for diagnostic confirmation in reference laboratories particularly for diagnosis of early disease with less than 7 days duration. This study provides a comprehensive evaluation of all currently available diagnostic tests for scrub typhus.

Functional implications of Drosophila insulin-like peptides in metabolism, aging, and dietary restriction.

The neuroendocrine architecture and insulin/insulin-like signaling (IIS) events in Drosophila are remarkably conserved. As IIS pathway governs growth and development, metabolism, reproduction, stress response, and longevity; temporal, spatial, and nutrient regulation of dilps encoding Drosophila insulin-like peptides (DILPs) provides potential mechanisms in modulating IIS. Of eight DILPs (DILP1-8) identified, recent studies have furthered our understanding of physiological roles of DILP2, DILP3, DILP5, and DILP6 in metabolism, aging, and responses to dietary restriction (DR), which will be the focus of this review. While the DILP producing IPCs of the brain secrete DILP2, 3, and 5, fat body produces DILP6. Identification of factors that influence dilp expression and DILP secretion has provided insight into the intricate regulatory mechanisms underlying transcriptional regulation of those genes and the activity of each peptide. Studies involving loss-of-function dilp mutations have defined the roles of DILP2 and DILP6 in carbohydrate and lipid metabolism, respectively. While DILP3 has been implicated to modulate lipid metabolism, a metabolic role for DILP5 is yet to be determined. Loss of dilp2 or adult fat body specific expression of dilp6 has been shown to extend lifespan, establishing their roles in longevity regulation. The exact role of DILP3 in aging awaits further clarification. While DILP5 has been shown associated with DR-mediated lifespan extension, contradictory evidence that precludes a direct involvement of DILP5 in DR exists. This review highlights recent findings on the importance of conserved DILPs in metabolic homeostasis, DR, and aging, providing strong evidence for the use of DILPs in modeling metabolic disorders such as diabetes and hyperinsulinemia in the fly that could further our understanding of the underlying processes and identify therapeutic strategies to treat them.