Diabetes mellitus is a risk factor for tuberculosis, but the underlying mechanisms remain unclear. We examined the host-Mycobacterium tuberculosis (Mtb) interaction in diabetes. Monocyte-derived macrophages from people with type 1 diabetes and healthy controls were infected with Mtb, and analyzed for host and Mtb gene expression and culture supernatant cytokines. Expression of antibacterial defense genes upon infection was mostly similar, but IFN-γ, both at RNA and protein level, was lower in macrophages from people with diabetes. Intracellular Mtb showed stress responses and a metabolic shutdown, both in macrophages from people with diabetes and controls. Expression of CYBB and other Mendelian susceptibility to mycobacterial disease genes strongly correlated with expression of Mtb cell wall and lipid genes in control macrophages, but much less so in diabetes. This rich dual RNA-seq dataset shows how type 1 diabetes may affect cross-talk between macrophages and Mtb, providing a valuable resource for future mechanistic studies.

Sepsis arises from a dysregulated immune response to infection, causing systemic inflammation and high mortality. Its nonspecific symptoms and complex molecular mechanisms make early diagnosis and therapeutic development challenging. The contribution of host factors to this heterogeneity is not fully understood. We investigated whether baseline gene co-expression networks are preserved or reorganized in sepsis and whether age and sex influence these networks by analyzing RNA-seq data from Peripheral Blood Mononuclear Cells (PBMCs) of healthy Romanian individuals and sepsis patients. Sixteen co-expression modules were identified in healthy controls. Most were preserved in sepsis, but four exhibited disrupted organization, indicating selective network reprogramming. Notably, the green module was strongly associated with age, sex, and sepsis. Within this module, 13 age-associated and 20 sex-associated hub genes were identified. Individual hub genes showed modest discriminative ability, whereas a multigene model achieved high accuracy (AUC = 0.988). Transcription factor motif enrichment highlighted STAT family and AP-1-related signals, while functional enrichment implicated chromatin remodeling, DNA repair, and immune pathways, consistent with hallmarks of aging. These results suggest that age and sex shape the molecular architecture of sepsis, emphasizing the need for demography-aware approaches to understand its biology and prioritize pathways and regulators for validation towards precision diagnostics and therapeutics.

The Bacillus Calmette-Guérin (BCG) vaccine, primarily designed for tuberculosis, exerts non-specific immunological effects that vary considerably among children. Limited knowledge exists regarding genetic variants that can impact immune responses post-vaccination. Understanding the genetic factors influencing the immune response in children following BCG vaccination is crucial for optimizing vaccine strategies. Genome-wide pQTL mapping of 65 circulating inflammatory proteins profiled at Month 13 uncovered 11 independent genome-wide significant loci. Following pQTL mapping in BCG-unvaccinated children, whose mean age was not significantly different from that of BCG-vaccinated children, a P-value lookup complemented with statistical colocalization and interaction analyses identified four pQTLs (rs10217747: CXCL11, rs13187850: CD6, rs56283092: LAP-TGF-beta 1, and rs11708321: CDCP1) showing evidence of genotype-by-BCG interactions and larger effect estimates in the BCG group. These variants have previously been associated with inflammatory and autoimmune traits. Genetic analysis of in vitro cytokine production capacity after BCG vaccination identified nominal associations mainly at Month 13 rather than Day 4 or Month 3. These findings enhance our understanding of immune responses to vaccination in children but, given the exploratory genome-wide approach, should be considered hypothesis-generating and require further validation.

A field experiment was conducted in the year 2023-24 at the main experimental station, ANDUAT, Ayodhya (eastern Uttar Pradesh, India) to determine the efficacy of different granular insecticides as a substitute to phorate 10% G in managing aphid population, reducing virus incidence and enhancing profits in potato crop variety Kufri Jyoti. There were a total of six treatments namely, fipronil 0.3% G, cartrap hydrochloride 4% G and phorate 10%G including control, which were incorporated in soil during earthing up in varying doses. Application of fipronil 0.3 % G @ 25 kg/ ha and cartrap hydrochloride 4% G @ 25 kg/ ha effectively reduced the aphid population by approximately 60% with consequent decrease in virus incidence by 45.9 and 42.9 %, respectively that resulted in increased tuber yield and better economic returns.

Hyperferritinemia is increasingly recognized as a marker of inflammation and severity in sepsis. This study aimed to ascertain the level of ferritin as a predictor of septic shock (SS) and its association with outcome. A prospective observational study was conducted on 123 children diagnosed with severe sepsis and SS at a tertiary care hospital of North India. Serum ferritin levels were measured, with hyperferritinemia defined as levels >500 ng/ml. Good outcome was defined as discharge or improving clinical status, and bad outcome was defined as death or clinical deterioration. The association of hyperferritinemia with SS and clinical outcomes was analyzed and statistically evaluated. Analysis of the area under the curve (AUC) and the receiver operating characteristic (ROC) curve was constructed to assess the predictive strength of ferritin as a marker of SS. Sensitivity, specificity, and positive and negative likelihood ratios were calculated at different cutoff values of serum ferritin. Hyperferritinemia was found in 66.6% of patients, with significantly higher levels in SS (1,624.67 ± 1,522.02 ng/ml) than sepsis (727.02 ± 1,081.12 ng/ml, p = 0.005). Hyperferritinemia (serum ferritin ≥ 730 ng/ml) was a predictor of SS (AUC = 0.80; 95% CI = 0.72-0.89; p value = 0.02). Mortality was higher in patients with hyperferritinemia (odd ratio = 12.9; 95% CI = 1.67-99.90; p value = 0.001). Serum ferritin at a level of 2,214 ng/ml was found to be predictive of secondary hemophagocytic lymphohistiocytosis (sensitivity of 100% and specificity of 94.8%). Hyperferritinemia is prevalent in pediatric sepsis and SS and is significantly associated with higher mortality. Serum ferritin may serve as a potential prognostic marker for identifying high-risk patients.

A significant proportion of individuals who are heavily exposed to infectious tuberculosis patients do not acquire Mycobacterium tuberculosis (Mtb) infection, as detected by an interferon gamma release assay (IGRA). We examined circulating metabolite profiles and metabolic genotypes in 199 heavily exposed IGRA-negative tuberculosis household contacts in Indonesia. Based on differentially abundant metabolites, activity of several pathways including arachidonic acid, arginine and proline, glutathione, and tryptophan metabolism, correlated with a negative IGRA at three months. SNPs near PRODH (involved in arginine and proline metabolism) were associated with circulating proline concentrations and persistently negative IGRA results, while SNPstudys near AFMID (involved in tryptophan metabolism) were associated with IGRA conversion. For further validation, plasma metabolomic profiles were correlated with mycobacterial growth inhibition by peripheral blood mononuclear cells from individuals in a low-incidence setting. Lower circulating concentrations of six metabolites, including leukotriene B4, proline, glycine, and tryptophan correlated with better growth control in non-exposed healthy individuals, as well as with stronger protection against IGRA-conversion in the Indonesian tuberculosis household contacts. Collectively, these data support the notion that circulating metabolites may impact innate host defense against Mtb infection, and that metabolic interventions may prevent tuberculosis infection and disease.

Heritage diets are disappearing as food systems homogenize; their effects on immunity, metabolism and host–microbiome biology remain poorly understood. The World Diet Initiative offers a framework to document heritage diets and investigate their effects before they are lost.

Bloodstream infection with Candida species is associated with high mortality, yet the molecular basis of vascular adhesion and invasion remains unclear. We identify the endothelial surface mucin MUC16 as a key host factor enabling fungal vascular adherence. The MUC16 SEA domain directly engages the Candida adhesin Als3p and endothelial N-cadherin to form a ternary complex that promotes endothelial attachment and vascular invasion. Genetic deletion of Muc16 in mice markedly reduced fungal vascular binding, renal fungal burden, and Ly6Ghi CD11b+ neutrophil recruitment following intravenous infection, and diminished oral colonization in an oral model. Inflammatory induction of MUC16 occurred via MINCLE-, TLR9-, and Dectin-1-dependent signaling, converging on CARD9. In clinical cohorts, a MUC16 T10155I variant and elevated circulating MUC16 were associated with increased 30-day mortality. These findings establish MUC16 as a mechanistic link between endothelial sensing and Candida vascular invasion, with prognostic relevance in candidemia.

The ability to assess and utilise the length of the daily light period has been identified as a key component of the physiological ecology regulating metabolism and reproduction across various vertebrate taxa. While light-dependent responses have been extensively studied, the ecological and physiological significance of natural darkness remains relatively less explicitly emphasized. In fact, studies investigating the role of light in controlling biological processes underscore that the period of darkness is an integral component of the light–dark cycle and an important ecological dimension in shaping the biology of organisms. Therefore, drawing largely from artificial light at night (ALAN) studies, this review synthesizes current evidence on how disruption of light–dark cycles, particularly the darkness at night, perturbs the circadian organization, with cascading effects on metabolism and reproduction, and how metabolism acts as a physiological gatekeeper of reproduction in diurnal vertebrates. Here, much of the evidence that we discuss is from both laboratory and field studies on diurnal birds. Importantly, we underscore the critical ecological value of the natural darkness within the 24-h day, emphasizing that the preservation of the night environment is crucial for maintaining the bioenergetic balance and population viability of species in an overly lit, urbanized environment.

Artificial dim light at night (dLAN) depresses the nocturnal melatonin peak, along with disruption to sleep and metabolism. This study asked whether exogenous melatonin administration could reverse the effects of dim light at night on sleep and metabolism in a diurnal songbird. To answer this, three groups of zebra finches (Taeniopygia guttata) of both sexes (n=6/group/sex) hatched and raised in our indoor aviary were used. While one group remained on the dark night (LD control; 12 h light:12 h dark, light 150 lx, dark 0 lx), as before, for the other two groups the 12 h dark night was replaced with 5 lx (equivalent to 0.048 W m-2) dim light (dLAN treatment; 12 h light:12 h dLAN). Half an hour before dark onset, consecutively for the next 11 days, the birds of one dLAN group received subcutaneous injections of melatonin (10 μg 100 μl-1 vehicle), while those of the other dLAN group and the LD group (controls) received 100 μl vehicle alone. Exogenous melatonin mitigated dLAN-induced disruptive effects on both nocturnal sleep and metabolism. As compared with the LD and vehicle-treated control birds, melatonin-treated birds showed a significantly reduced nocturnal sleep frequency (fewer awakenings) and longer sleep bout as well as reduced night-time feeding and body fattening, and restoration of normal hepatic expression of genes associated with glucose and lipid metabolism. In particular, the elevated melatonin levels prevented the midnight increase in expression of g6pc, irs1, fasn, star and egr1, and augmented the sirt1 mRNA levels under the dLAN environment. These results suggest that nocturnal melatonin levels are a crucial component of the regulatory pathways underlying nocturnal sleep and metabolism, independent of sex, in a diurnal songbird species.

This study examines the role of host inflammation in the high mortality of tuberculous meningitis (TBM) and identifies potential biomarkers associated with improved survival. We conducted a case-control study involving 131 patients in a discovery cohort, 81 TBM patients in a validation cohort, and 43 non-infected controls from a referral hospital in Indonesia. We measured 94 inflammation-related proteins in cerebrospinal fluid (CSF) and performed genome-wide quantitative trait loci (QTL) mapping. Sixty-seven proteins were found to be differentially expressed between TBM patients and controls, with 64 proteins elevated in patients. Five proteins, including vascular endothelial growth factor (VEGF) and matrix metalloproteinase-10 (MMP-10), were identified as predictors of 180-day mortality in TBM patients. The validation cohort confirmed that MMP-10, but not VEGF, was predictive of mortality. Genome-wide QTL mapping identified two genome-wide significant and four suggestive genetic loci associated with CSF MMP-10, which also predicted survival in an additional cohort of 218 patients. High CSF concentrations of MMP-10, along with specific genetic loci, may be associated with survival in TBM patients, suggesting a potential role for MMP-10 in disease pathogenesis and warranting further investigation into its utility in host-directed therapies.

To most, if not all, species, the food availability shows both daily and seasonal fluctuations in its timing, quality, and abundance. Hence, coupled with the appetite (urge to eat), it results in species-specific foraging (eating or feeding) patterns, an ecological determinant of almost all the aspects of behavior and physiology in animals. The feeding times control mutually inclusive physiological events by affecting metabolic homeostasis (a direct effect) and/ or by their synchronization effects on the underlying circadian rhythms (an indirect effect). Experiments have shown that food intake at an inappropriate time of the day (i.e., at a wrong time relative to the internal circadian clock) negatively affects the circadian homeostasis and consequently the behavior, metabolism and reproduction in animals. The food availability times as a conditioning environment influence epigenetics, evidenced by chromatin activation/ silencing at genome levels in several species. Here, we review briefly the experimental evidence largely from birds and mammals to provide insights into when and how daily feeding times affect the clock-controlled behavior, metabolism and reproductive fitness in diurnal species.

Illuminated nights reduce melatonin peak and disrupt sleep. Using this as the basis of the present experimental paradigm, we investigated whether nocturnal melatonin levels were crucial for sleep regulation in a diurnal vertebrate. Acclimated Indian house crows ( Corvus splendens ) were randomly segregated into three groups of 12 each. For the next 10 days, one group was maintained on 12 L:12 D, as before (LD control); for the other two groups, the absolute darkness was replaced with dim light at night (dLAN; L = ~150 lux, D = ~6 lux). Under dLAN, half an hour before light off time, the LD control and one dLAN group received intraperitoneally 200 μL of vehicle (0.75% physiological saline), while the other dLAN group received a similar 200 μL vehicle but containing melatonin at a dose of 50 μg bird −1 day −1 . Under dLAN, exogenous melatonin elevated nocturnal AANAT mRNA and plasma melatonin levels and induced changes in diurnal expressions of clock genes ( PER2 , CRY1 , BMAL1 , NPAS2 , REVERB ) in the pineal gland and hypothalamus, and of genes encoding melatonin receptors ( MEL1a , MEL1b ) and epigenetic modifiers ( HAT1 , HDAC2 , HDAC4 , DNMT3a ) in the hypothalamus. Elevated nocturnal melatonin levels bettered sleep with positive effects on the hypothalamic expression of genes associated with nocturnal sleep (cytokine pathway: TLR4 , TNFα , IL‐1β , NOS1 ; calcium pathway: CAMK2 , SIK3 ) and awake ( ACHM3 , EGR1 , HOMER1a , OREXIN ) states, and with neurogenesis and synaptic plasticity ( BDNF , EGR1 , CREB ). These suggested the role of melatonin in mitigation of the dLAN‐induced sleep disruption. Nocturnal melatonin peak levels are a crucial component of the regulatory transcriptional pathways underlying the daily wake–sleep pattern, with far‐reaching implications for sleep‐related issues in diurnal species including perhaps humans inhabiting an over‐lit environment with pervasive light pollution.

Cryptococcus neoformans , Cryptococcus gattii and Candida albicans are opportunistic fungal pathogens associated with infections in immunocompromised hosts. Cryptococcal meningitis (CM) is the leading fungal cause of HIV-related deaths globally, with the majority occurring in Africa. The human immune response to C. albicans infection has been studied extensively in large genomics studies whereas cryptococcal infections, despite their severity, are comparatively understudied. Here we investigated the transcriptional response of immune cells after in vitro stimulation with in vitro C. neoformans , C. gattii and C. albicans infection of peripheral blood mononuclear cells (PBMCs) collected from healthy South African volunteers. We found a lower transcriptional response to cryptococcal stimuli compared to C. albicans and unique expression signatures from all three fungal stimuli. This work provides a starting point for further studies comparing the transcriptional signature of CM in immunocompromised patients, with the goal of identifying biomarkers of disease severity and possible novel treatment targets.

Exposure to dim light at night (dLAN) affects circadian rhythms and disrupts sleep and metabolism. However, given differential light sensitivity of circadian rhythms during early and late hours of the night, dLAN may have dissimilar detrimental effects in two halves of the night. If so, the disruptive effects of dLAN would be mitigated at different levels if one of the two halves of the night were replaced by complete darkness. We investigated this using both sexes of diurnal zebra finches that were exposed for three weeks to 12 h light ( 150 lx) coupled with 12 h dark (0 lx), dLAN (5 lx), and half-dark and half-dLAN (6 h dark + 6 h dLAN, or vice versa) nights. dLAN disrupted the nocturnal sleep (shorter sleep bouts, reduced nocturnal sleep with frequent awakenings), and impaired glucose and fat metabolism as evidenced by body fattening and concurrent increase in g6pc, irs1 and star, and decrease in glut5 and sirt1 gene expressions in the liver. The substitution of half of dLAN with complete darkness mitigated much of the negative effects, with a much better alleviative response when the imposed darkness period covered the first half of the 12 h ‘dLAN’ night. Notably, the mitigation effects of darkness period were sex dependent. These results provide insights into differential temporal sensitivity of the night to negative impacts of the emerging ‘light pollution’ threat in an over-lit urban environment.

Artificial light at night (ALAN) is a growing environmental pollutant with significant risks to brain health in both animals and humans. This study assessed the ALAN-induced negative impact and examined potential mitigative strategies on neurobehavioural traits and associated neural pathways in diurnal Indian house crows subjected to dim light at night (dLAN, 6 lx) in a 12-hour:12-hour light-dark cycle. The 12-hour dLAN period was either interrupted midway by a 2-hour dark period (controls in 0 lx dark night; experiment 1) or preceded by a 50 µg day⁻¹ crow⁻¹ melatonin pre-treatment 30 min before the dLAN onset (controls received vehicle; experiment 2). dLAN exposure reduced nocturnal melatonin levels, and negatively impacted the circadian behaviour, sleep, mood and cognitive performance as well as the mRNA expression of genes associated with neurogenesis (bdnf, dcx, nr4a2), neuroinflammation (tnfα and tnfr1), and epigenetic regulation (hat1, hdac2, hdac4) in hippocampus and nidopallium caudolaterale brain regions. The midnight 2-hour dark period partially restored, but the evening melatonin pre-treatment completely restored the dLAN-induced disrupted neurobehaviours and associated gene expressions. These results provide mechanistic insights into night-light pollution effects, and suggest a pivotal role of melatonin in preserving the sleep integrity and cognitive functions in animals, perhaps also in humans.

Artificial light at night (LAN) reduces the natural darkness and negatively impacts behavior, physiology, and higher brain functions in both captive and wild animals. The inevitable widespread usage of LAN exposure is usually from the broad spectrum dim LAN (dLAN). Here, we investigated whether a monochromatic light would affect the dLAN-induced effects on sleep, metabolism and oxidative stress in a diurnal vertebrate, the zebra finch (Taeniopygia guttata). Birds were maintained on 12 h of broad-spectrum light (150 lux, 1.426 W/m²) coupled with 12 h of complete dark night or dLAN at an identical intensity (5 lux, 0.048 W/m²) of broad spectrum (400-700 nm), long (620 nm) and short (460 nm) light wavelengths. Light wavelengths affected the dLAN-induced intermittent awakenings and advanced morning wakeups, hence a shorter and poorer sleep, with concurrent changes in the hypothalamic gene expression patterns. In particular, the mRNA expressions of sik3 and achm3 genes were consistent with wavelength effects on the awake state promotion, and those of dcx and bdnf genes were consistent with the sleep deprivation effects on the overall brain functioning. Further, dLAN-induced nocturnal feeding resulted in body fattening and weight gain, suggesting metabolic impairment in the broad spectrum and short wavelength but not the long wavelength dLAN. There were increased nocturnal hepatic g6pc and irs1 mRNA levels, indicating an elevated gluconeogenesis in both broad spectrum and short wavelength dLAN. We also found an enhanced oxidative stress, evidenced by elevated gpx and cat mRNA levels in the hypothalamus and blood, respectively, under both broad spectrum and short wavelength dLAN. These results highlight the wavelength-dependent effects of dLAN on sleep, metabolism, and oxidative stress in zebra finches, offering important insights into the broader consequences of nighttime light pollution for diurnal species, including humans inadvertently exposed to artificially lit urban environments.

Synchronization of physiological and behavioral activities associated with avian reproduction requires corresponding changes in the activity of the hypothalamus-pituitary-gonadal axis. This involves complex brain peptidergic pathways, which show spatial and temporal differences in their expression and distribution during the annual reproductive cycle. The well-studied pathways include gonadotropin-releasing and inhibiting hormones (GnRH, GnIH), neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART), vasoactive intestinal peptide (VIP) and other peptides like arginine vasotocin (VT), oxytocin (mesotocin), and spexin. Together, these peptides form a neurochemical framework for the integration of both internal and external (environmental) cues; this results in a neuroendocrine response. Conceivably, therefore, the neurochemical framework within which brain peptides possibly interact and perform reproductive regulatory roles might show species differences. Here, we aim to review briefly the roles of these neuropeptides in reproduction in both opportunistically and seasonally breeding birds. Much of the discussion will be based on our own research on the opportunistic breeding zebra finch and the seasonally breeding redheaded bunting, Indian weaverbird, and spotted munia. The summer breeding redheaded bunting and weaverbird are typical photosensitive long-day species, but they show qualitative differences in response to stimulatory photoperiods during the post-reproductive period of their annual cycle. Buntings exhibit absolute photorefractoriness, while weaverbirds exhibit relative photorefractoriness. The autumn breeding spotted munia, on the other hand, is an atypical photosensitive species. It responds to both short and long photoperiods and presumably lacks photorefractoriness.

The survival advantage of group living remains poorly understood. Here, this was investigated by using several physiological and neurobehavioral traits in Indian house crows (Corvus splendens) in the face of a temporally disrupted day-night environment. Crows were housed singly or with two other conspecifics and subjected to daily 12-h light and 12-h periods of complete (0 lx) or dimly lighted (∼6 lx) dark nights. Nocturnal melatonin and sleep levels were measured as indices of the direct and circadian effects, while mood (feeding, preening, and self-mutilation) and cognition (innovative problem-solving task) performances were considered reflecting the higher-order brain function effects. Under 6-lx dim light at night (dLAN) condition, group housing alleviated the depressive-like responses and enhanced cognitive performance but had no effect on the midnight melatonin levels and nocturnal sleep consolidation. Concurrently, there were increased nr4a2 and decreased tnfr1 gene expressions in hippocampus, increased dcx and darpp-32 gene expressions in the nidopallium caudolaterale, and th expression in midbrain. We interpret that an increased conspecific interaction improved mood and cognitive performance without affecting the melatonin secretion and sleep in communally roosting house crows. Perhaps, living with conspecifics is part of an overall evolutionary strategy to enhance the survival in a highly social species like the Indian house crow.